TWI768461B - Novel immunotherapy against several tumors including gastrointestinal and gastric cancer - Google Patents

Abstract

The present invention relates to peptides, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated cytotoxic T cell (CTL) peptide epitopes, alone or in combination with other tumor-associated peptides that serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses. The present invention relates to 95 novel peptide sequences and their variants derived from HLA class I molecules of human tumor cells that can be used in vaccine compositions for eliciting anti-tumor immune responses.

Description

Novel immunotherapy for several tumors including gastrointestinal and gastric cancers

The present invention relates to peptides, nucleic acids and cells for use in immunotherapy methods. In particular, the present invention relates to immunotherapy of cancer. The present invention also relates to tumor-associated cytotoxic T helper cell (CTL) peptide epitopes used alone or in combination with other tumor-associated peptides (active pharmaceutical ingredients of vaccine complexes that stimulate anti-tumor immune responses). The present invention relates to 33 novel peptide sequences and variants thereof derived from human tumor HLA class I molecules that can be used in vaccine compositions to elicit anti-tumor immune responses.

Gastric cancer is a disease in which malignant cells form in the stomach wall. Stomach cancer can develop in any part of the stomach and may spread throughout the stomach and other organs; especially the esophagus, lungs, and liver. Gastric cancer is the fourth most common cancer worldwide, with 930,000 diagnosed cases in 2002. Gastric cancer has a high mortality rate (~800,000 per year), making it the second most common cause of cancer death globally after lung cancer. The disease is more common in men and more common in Asian and developing countries. (http://www.who.int/mediacentre/factsheets/fs297/en/.) Gastric cancer accounts for about 2% (25,500) of all new cancer cases each year in the United States, but is more common in other countries. In Korea, gastric cancer is the number one cancer, accounting for 20.8% of malignant tumors. In Japan, gastric cancer remains the most common cancer in men. In the United States, approximately 8,000 men and 13,000 women are diagnosed with gastric cancer each year. Most are over 70 years old. Gastric cancer is the fourth most common cancer worldwide, after lung, breast, colon and rectal cancers. In addition, gastric cancer remains the second most common cause of cancer death. The American Cancer Society estimates that there were one million new cases in 2007, nearly 70% of which occurred in developing countries, and about 800,000 deaths (http://www.cancer.org/downloads/STT/Global_Facts_and_ Figures_2007_rev2.pdf .) There are large geographic differences in the global incidence of the disease. The incidence of the disease is highest in parts of Asia and South America and lowest in North America. The disease has recorded the highest mortality rates in Chile, Japan, South America and the former Soviet Union. Screening is not performed in most parts of the world, except for early detection, which is usually done in Japan (and in a limited fashion in Korea), so gastric cancer is usually diagnosed at an advanced stage. Thus, gastric cancer remains a major challenge for healthcare professionals. Risk factors for gastric cancer are Helicobacter pylori (H. pylori) infection, smoking, high salt intake, and other dietary factors. A minority of gastric cancers (1% to 3%) are associated with gastric cancer genetic predisposition syndrome. About 25% of families with autosomal dominant susceptibility to diffuse gastric cancer have mutations in the E-cadherin gene. This subgroup of gastric cancer is called hereditary diffuse gastric cancer. 12 It may be beneficial to provide genetic counseling and consider prophylactic gastrectomy in young asymptomatic carriers of germline truncation The stomach wall consists of 3 layers of tissue: the mucosal (innermost) layer, the muscular (middle) layer, and the serosa (outermost) layer. Gastric cancer first develops in the lining of the mucosal layer and spreads to the outer layers as it grows. There are four standard treatments for stomach cancer. Treatment options for gastric cancer include surgery, chemotherapy, radiation, or chemoradiotherapy. Surgery is the main treatment for gastric cancer. The goal of surgery is to perform a complete resection with negative margins (R0 resection). However, R0 resection cannot be performed in approximately 50% of localized gastric cancers. R1 resection indicates that residual cancer cells are visible under the microscope (positive margins), and R2 resection indicates that there are residual cancer cells visible to the naked eye, but the disease has not metastasized to distant sites. Patient outcomes depend on the initial stage found at diagnosis (NCCN Clinical Practice Guidelines in Oncology™). Five-year survival rates after curative surgical resection are 30-50% for patients with stage II disease and 10-25% for patients with stage II disease. These patients have an extremely high likelihood of local and systemic recurrence. 80-90% of gastric cancer patients will develop metastasis, the 6-month survival rate is 65% in patients diagnosed at an earlier stage, and less than 15% in patients diagnosed at a later stage. Therefore, there remains a need for novel treatment options that are safe and effective, and improve well-being without the use of chemotherapy drugs or drugs that can cause severe side effects in patients with the following cancers: gastric cancer, prostate (epithelial) cancer, oral cancer, oral squamous cell carcinoma squamous cell carcinoma (OSCC), acute myeloid leukemia (AML), MALT lymphoma caused by Helicobacter pylori, colon (epithelial)/colorectal cancer, glioblastoma, non-small cell lung cancer (NSCLC), cervical (epithelial) ) cancer, human breast cancer, prostate cancer, colon cancer, pancreatic cancer, pancreatic ductal adenocarcinoma, ovarian cancer, hepatocellular carcinoma, liver cancer, brain tumors of different phenotypes, acute lymphoblastic leukemia (ALL) and other leukemias, lung cancers , Ewing's sarcoma, endometrial cancer, head and neck squamous cell carcinoma, laryngeal epithelial cancer, esophageal cancer, oral (epithelial) cancer, bladder cancer, ovarian (epithelial) cancer, renal cell carcinoma, atypical meningioma, nipple thyroid cancer, brain tumor, salivary duct carcinoma, cervical cancer, extranodal T/NK cell lymphoma, non-Hodgkin lymphoma, malignant solid tumors such as lung and breast cancer, and other tumors. The present invention employs peptides that stimulate the immune system to act as anti-tumor agents in a non-invasive manner.

The ability to stimulate an immune response depends on the presence of antigens that are considered foreign by the host immune system. The discovery of the presence of tumor-associated antigens raises the possibility of using the host immune system to intervene in tumor growth. For cancer immunotherapy, various mechanisms that exploit the humoral and cellular immunity of the immune system are currently being explored. Certain elements of the cellular immune response specifically recognize and destroy tumor cells. Cytotoxic T-cells (CTL) isolated from tumor-infiltrating cell populations or peripheral blood suggest that these cells play an important role in the innate immune defense of cancer. In particular, CD8-positive T cells (TCD8 ⁺ ) play an important role in this response, and TCD8 ⁺ recognizes major tissue phases that are typically 8 to 10 amino acid residues derived from proteins or from defective ribosomal products (DRIPs) located in the cytoplasm. Class I molecules contained in peptides contained in a cytosolic complex (MHC). Human MHC molecules are also known as human leukocyte-antigens (HLA). There are two classes of MHC molecules: MHC class I molecules that are found on most cells with a nucleus. The MHC molecule consists of an alpha heavy chain and beta-2-microglobulin (MHC class I receptors) or alpha and beta chains (MHC class II receptors), respectively. Its three-dimensional configuration forms a binding groove for non-covalent interactions with peptides. MHC class I molecules present mainly endogenous proteins, DRIPS, and peptides resulting from the cleavage of larger peptides. MHC class II molecules are primarily found on professional antigen presenting cells (APCs) and present primarily peptides of exogenous or transmembrane proteins that are occupied by APCs during endocytosis and subsequently processed. The complexes of peptides and MHC class I molecules are recognized by CD8-positive cytotoxic T lymphocytes loaded with the corresponding TCRs (T cell receptors), while the complexes of peptides and MHC class II molecules are carried out by CD4-positive helper T cells loaded with the corresponding TCRs. identify. It is well known in the art that TCR, peptide and MHC are thus present in stoichiometric amounts of 1:1:1. For a peptide to trigger (elicit) a cellular immune response, it must bind to an MHC molecule. This process depends on the alleles of the MHC molecule and the specific polymorphisms of the amino acid sequence of the peptide. MHC-class I-binding peptides are typically 8-12 amino acid residues in length and typically contain two conserved residues ("anchors") in their sequences that interact with the corresponding binding grooves of the MHC molecule. In this way, each MHC allele has a "binding motif" that determines which peptides can specifically bind to the binding groove. In an MHC-class I-dependent immune response, not only can peptides bind to certain MHC-class I molecules expressed by tumor cells, but they must also be recognized by T-cell-specific T-cell receptors (TCRs). Antigens recognized by tumor-specific cytotoxic T lymphocytes, i.e. their epitopes, can be molecules derived from all protein types, such as enzymes, receptors, transcription factors, etc., which are expressed in the cells of the corresponding tumor, and Its expression is up-regulated compared to homologous unaltered cells. Tumor-associated peptides are currently classified into the following main groups: a) Cancer-testis antigens: The first identified TAAs recognized by T cells belong to this class of antigens, as their members are expressed in histologically distinct human tumors, normal tissues In, only in spermatocytes/spermatogonia of the testis, and occasionally in the placenta, so it was originally called the cancer-testis (CT) antigen. Since testicular cells do not express HLA class I and II molecules, these antigens cannot be recognized by T cells in normal tissues, and thus can be considered immunologically tumor-specific. A well-known example of a CT antigen is a member of the MAGE family or NY-ESO-1. b) Differentiation antigens: Both tumor and normal tissue from which the tumor is derived contain TAA, most of which are found in melanoma and normal melanocytes. Many of these melanocyte lineage-associated proteins are involved in melanin biosynthesis, so these proteins are not tumor-specific, but are still widely used in cancer immunotherapy. Examples include, but are not limited to, tyrosinase for melanoma and Melan-A/MART-1 or PSA for prostate cancer. c) Overexpressed TAAs: Genes encoding widely expressed TAAs have been detected in histologically distinct tumors as well as in many normal tissues, generally at low levels. It is possible that many epitopes processed and potentially presented by normal tissues are below the threshold level for T cell recognition, and their overexpression in tumor cells can elicit anticancer responses by breaking previously established tolerance. Typical examples of such TAAs are Her-2/neu, survivin, telomerase or WT1. d) Tumor-specific antigens: These unique TAAs arise from mutations in normal genes (eg, calcium-catenin, CDK4, etc.). Some of these molecular changes are associated with tumorigenic transformation and/or progression. Tumor-specific antigens generally induce strong immune responses without the risk of an autologous immune response to normal tissues. On the other hand, these TAAs are in most cases only associated with the exact tumors on which TAAs have been identified, and TAAs are often not shared among many individual tumors. e) TAAs produced by aberrant post-translational modifications: Such TAAs may be produced by proteins that are neither specific nor overexpressed in the tumor, but which still have tumor relevance (the correlation is determined by translations that are primarily active against the tumor) post-processing). Such TAAs arise from alterations in variable glycosylation patterns, leading tumors to develop novel epitopes against MUC1 or leading to events such as protein splicing during degradation, which may or may not be tumor specific. f) Tumor viral proteins: These TTAs are viral proteins that can play a key role in carcinogenesis and since they are foreign proteins (non-human proteins), they are capable of eliciting T cell responses. Examples of such proteins are the human papilloma type 16 virus proteins, E6 and E7, which are expressed in cervical cancer. Special conditions must be met for proteins to be recognized by cytotoxic T lymphocytes as tumor-specific or associated antigens and for use in therapy. The antigen should be expressed predominantly by tumor cells and not by normal healthy tissue, or in a relatively small amount. More suitably, the corresponding antigen is not only present in one tumor but also in high concentration (ie the number of copies of the corresponding peptide per cell). Tumor-specific and tumor-associated antigens are often derived from proteins directly involved in the normal-to-tumor cell transformation that occurs as a result of a function in cell cycle control or apoptosis inhibition. In addition, downstream targets of these proteins that directly lead to transformation events may be up-regulated and thus may be indirectly associated with tumors. These tumor-associated antigens may also be targets for vaccination approaches (Singh-Jasuja H., Emmerich NP, Rammensee HG, Cancer Immunol. Immunother. 2004 Mar; 453(3):187-95). In both cases, it is critical that epitopes of the antigenic amino acid sequence are present, so that such peptides from tumor-associated antigens ("immunogenic peptides") can elicit T cell responses in vitro or in vivo. Basically, any peptide that can bind to an MHC molecule might act as a T-cell epitope. A prerequisite for inducing a T cell response in vitro or in vivo is the presence of T cells with the corresponding TCR and the absence of immune tolerance to that particular epitope. Therefore, TAA is the starting point for the development of tumor vaccines. Methods for identifying and characterizing TAAs are based on the use of CTLs in patients or healthy subjects, or on the generation of differential transcriptional properties or differential expression patterns between tumor and normal tissue peptides. However, the identification of genes that are overexpressed or selectively expressed in tumor tissues or human tumor cell lines does not provide accurate information on the antigens transcribed by these genes for use in immunotherapy. This is because T cells with the corresponding TCR must be present and immune tolerance to this particular epitope must be non-existent or minimal, so only a subset of these antigenic epitopes are suitable for this application. Therefore, it is very important to select only those peptides whose proteins are overexpressed or selectively expressed, and that these peptides are presented in conjunction with MHC molecules that can find resistance to functional T cells. Such functional T cells are defined as T cells capable of clonally expanding and capable of performing effector functions ("effector T cells") upon stimulation with a specific antigen. Helper T cells play an important role in orchestrating CTL effector functions for antitumor immunity. Helper T cell epitopes that trigger _TH1 cell responses support the effector functions of CD8-positive killer T cells, including cytotoxicity directly on tumor cells that display tumor-associated peptide/MHC complexes on their surface. Thus, tumor-associated T helper cell peptide epitopes, alone or in combination with other tumor-associated peptides, can be used as active pharmaceutical ingredients in vaccine compositions that stimulate anti-tumor immune responses.

Unless otherwise specified, all terms used herein are defined below. The term "peptide", as used herein, refers to a series of amino acid residues, usually interconnected by peptide bonds between the alpha-amino acid and the carbonyl groups of adjacent amino acids. These peptides are preferably 9 amino acids in length, but can be as short as 8 amino acids in length and as long as 10, 11, 12, 13 or 14 amino acids in length. The term "oligopeptide" as used herein refers to a series of amino acid residues, usually interconnected by peptide bonds between the alpha-amino acid and the carbonyl groups of adjacent amino acids. The length of the oligopeptide is not critical to the present invention as long as the correct epitope is maintained in the oligopeptide. Typically, oligopeptides are less than about 30 amino acid residues and longer than about 14 amino acids in length. The term "polypeptide" refers to a series of amino acid residues, usually interconnected by peptide bonds between the alpha-amino acid and the carbonyl groups of adjacent amino acids. The length of the polypeptide is not critical to the present invention as long as the correct epitope is maintained. In contrast to the terms peptide or oligopeptide, the term "polypeptide" refers to a molecule comprising more than about 30 amino acid residues. A peptide, oligopeptide, protein, or nucleotide encoding the molecule is "immunogenic" if it induces an immune response (hence an "immunogen" in the present invention). In the context of the present invention, a more specific definition of immunogenicity is the ability to induce a T cell response. Thus, an "immunogen" is a molecule capable of inducing an immune response, and in the context of the present invention, a molecule capable of inducing a T cell response. What the T cell "epitope" requires is a short peptide that binds to MHC class I receptors, thereby forming a ternary complex (MHC class alpha chain, beta-2-microglobulin, and peptide) that can be Recognition by a T cell with the corresponding affinity binding to the matched T cell receptor of the MHC/peptide complex. Peptides bound to MHC class I molecules are typically 8-14 amino acids in length, most typically 9 amino acids in length. In humans, there are three distinct loci encoding MHC class I molecules (human MHC molecules are also designated human leukocyte antigens (HLA)): HLA-A, HLA-B, and HLA-C. HLA-A*01, HLA-A*02, and HLA-A*024 are examples of different MHC class I alleles that can be expressed from these loci. Table 1: Expression frequency F of HLA-A*024 and the most common HLA*A02402 serotypes. Frequency according to the Hardy-Weinberg formula used by Mori et al. (Mori et al. 1017-27) F=1-(1-G_f )² adapted from US population-wide haplotype frequencies. For details, see Chanock et al. (Chanock et al. 1211-23). Expression frequencies of global serotypes HLA*24 and A*2402 allele crowd Phenotypes based on allele frequencies A*24 Filipino 65% A*24 Russian Nenets 61% A*2402 Japanese 59% A*24 Malaysian 58% A*2402 Filipino 54% A*24 Indian 47% A*24 Korean 40% A*24 Sri Lankan 37% A*24 Chinese 32% A*2402 Indian 29% A*24 Western Australian twenty two% A*24 American twenty two% A*24 Russian Samara 20% A*24 South American 20% A*24 European 18% The DNA sequences referred to herein include both single-stranded DNA and double-stranded DNA. Thus, unless otherwise indicated herein, a specific sequence is the single-stranded DNA of that sequence, the duplex (double-stranded DNA) of that sequence and its complement, and the complement of that sequence. The term "coding region" refers to that portion of a gene that naturally or normally encodes the expression product of the gene in its native genomic environment, ie, the region that encodes the native expression product of the gene in vivo. Coding regions can be derived from non-mutated ("normal") genes, mutated or abnormal genes, or even DNA sequences, and can be synthesized in the laboratory using DNA synthesis methods well known in the art. The term "nucleotide sequence" refers to a heteropolymer of deoxynucleotides. The nucleotide sequence encoding a particular peptide, oligopeptide or polypeptide can be a natural nucleotide sequence or a synthetic nucleotide sequence. Generally, DNA fragments encoding peptides, polypeptides, and proteins of the invention consist of cDNA fragments and short oligonucleotide linkers, or a series of oligonucleotides, to provide a synthetic gene capable of Or the regulatory elements of the viral operon are expressed in recombinant transcription units. The term "expression product" refers to a polypeptide or protein that is the translation product of any nucleic acid sequence encoding an equivalent resulting from the degeneration of the gene and genetic code and thus encoding the same amino acid. The term "fragment", when referring to a coding sequence, refers to a portion of DNA comprising an incomplete coding region, the expression product of which has substantially the same biological function or activity as the expression product of the complete coding region. The term "DNA fragment" refers to a DNA polymer, in the form of individual fragments or components of a larger DNA structure, obtained in substantially pure form, i.e. free from DNA that has been isolated at least once Contaminating endogenous material, and the resulting amounts or concentrations enable identification, manipulation and recovery of the fragment and its component nucleotide sequences using standard biochemical methods, such as the use of cloning vectors. These fragments exist as open reading frames (uninterrupted by internal untranslated sequences) or introns (usually presented in eukaryotic genes). Untranslated DNA sequences may exist downstream of the open reading frame where they do not interfere with the manipulation or expression of the coding region. The term "primer" refers to a short nucleic acid sequence that can pair with a DNA strand and provide a free 3'-OH terminus where DNA polymerase begins to synthesize the deoxyribonucleic acid strand. The term "promoter" refers to the region of DNA involved in the binding of RNA polymerase to initiate transcription. The term "isolated" means that a substance is removed from its original environment (eg, the natural environment if it occurs in nature). For example, native nucleotides or polypeptides in living animals are not isolated, but nucleotides or polypeptides that are isolated from some or all coexisting species in the native system are isolated. Such polynucleotides may be part of a vector and/or such polynucleotides and polypeptides may be part of a composition, and since the vector or composition is not part of its natural environment, it remains isolated. The polynucleotides and recombinant or immunogenic polypeptides disclosed in the present invention may also exist in "purified" form. The term "purified" does not require absolute purity; it is only a relative definition and can include highly purified or partially purified preparations, as those terms are understood by those skilled in the relevant art. For example, each clone is isolated from a cDNA library that has been purified by conventional methods to be electrophoretically homogenous. It is expressly contemplated to purify the starting material or natural substance by at least one order of magnitude, preferably two or three orders of magnitude, more preferably four or five orders of magnitude. Furthermore, it is expressly contemplated that the purity of the polypeptide is preferably 99.999%, or at least 99.99% or 99.9%; even suitably 99% by weight or higher. Nucleic acid and polypeptide expression products disclosed in accordance with the present invention, as well as expression vectors comprising such nucleic acids and/or polypeptides, may exist in "concentrated form". The term "concentrated" as used herein refers to a concentration of a material that is at least about 2, 5, 10, 100 or 1000 times its natural concentration, advantageously 0.01% by weight, preferably at least 0.1%. Concentrated formulations of about 0.5%, 1%, 5%, 10% and 20% by weight are also expressly contemplated. Sequences, configurations, vectors, clones, and other materials comprising the present invention may advantageously exist in concentrated or isolated form. The term "active fragment" refers to a fragment that produces an immune response (ie, has immunogenic activity), whether administered alone or optionally with a suitable adjuvant to an animal, such as a mammal, such as a rabbit or a mouse, Humans are also included; this immune response takes the form of stimulating a T-cell response in a recipient animal (eg, a human). Alternatively, "active fragments" can also be used to induce T cell responses in vitro. The terms "portion," "segment," "fragment," as used herein, when used in relation to a polypeptide, refer to a contiguous sequence of residues, such as amino acid residues, which Sequences form a subset of a larger sequence. For example, if a polypeptide is treated with any of the endopeptidase enzymes (eg, trypsin or chymotrypsin), the oligopeptide obtained from the treatment will represent a portion, segment, or fragment of the starting polypeptide. This means that any such fragment must contain as part of its amino acid sequence a segment, fragment or part that is substantially identical (if not identical) to the sequence of SEQ ID NOs: 1 to 33, which corresponds to SEQ ID NOs: 1 to 33 The native or "parent" protein of 33. When used in relation to a polynucleotide, these terms refer to the product resulting from treatment of the polynucleotide with any common endonuclease. According to the present invention, the term "percent equivalence" or "percent equivalence", if referring to a sequence, means between the sequence to be compared ("compared sequence") and the sequence of said or claimed sequence ("reference sequence") Following alignment, the compared sequences are compared to the sequence or the claimed sequence. The percent equivalence is then calculated according to the following formula: Percent Equivalence = 100 [I-(C/R)] where C is the number of differences between the reference and compared sequences in the alignment length between the reference and compared sequences, where (i) each base or amino acid sequence in the reference sequence has no corresponding alignment base or amino acid in the sequence being compared; (ii) each gap in the reference sequence, and (iii) each alignment base or amino acid in the reference sequence is different from the alignment base or amino acid in the aligned sequence, i.e. constitutes a difference; and R is the alignment length between the reference sequence and the aligned sequence in the reference sequence Any gaps created are also counted as the number of bases or amino acids in the reference sequence for one base or amino acid. A compared sequence has a specified minimum percent identity to the reference sequence if there exists an alignment between the "aligned sequence" and the "reference sequence" whose percent identity calculated above is approximately equal to or greater than the specified minimum percent identity , although there may be alignments where the percent equivalence calculated as described above is lower than the specified percent equivalence. If not stated otherwise, the original peptides disclosed herein may be modified by substituting one or more residues at different (possibly selective) sites within the peptide chain. Such substitutions may be conservative, eg, where one amino acid is replaced by another amino acid of similar structure and characteristics, such as where one hydrophobic amino acid is replaced by another hydrophobic amino acid. More conservative substitutions are those between amino acids of the same or similar size and chemistry, eg, leucine is replaced by isoleucine. In studies of sequence variation in natural homologous protein families, substitutions of certain amino acids tend to be more tolerated than others, and these amino acids tend to show similarities between the size, charge, polarity, and hydrophobicity of the original amino acid. , which is the basis for determining "conservative substitution". In this context, conservative substitution is defined as an exchange within one of the following five groups: group 1 - a small aliphatic, non-polar or slightly polar residue (Ala, Ser, Thr, Pro, Gly); Group 2-polar, negatively charged residues and their amides (Asp, Asn, Glu, Gln); Group 3-polar, positively charged residues (His, Arg, Lys); Group 4- Large aliphatic nonpolar residues (Met, Leu, Ile, Val, Cys) and group 5-large aromatic residues (Phe, Tyr, Trp). Less conservative substitutions may involve the replacement of one amino acid by another amino acid with similar characteristics but different in size, eg, alanine is replaced by an isoleucine residue. Highly non-conservative substitutions may involve the replacement of an acidic amino acid by another amino acid with polar or even basic properties. However, such "radical" substitutions cannot be dismissed as ineffective because chemical effects are not completely predictable, and radical substitutions may have contingent effects unforeseeable in their simple chemical principles. Of course, such substitutions may involve other structures than ordinary L-amino acids. Therefore, D-amino acids may be substituted by L-amino acids commonly found in the antigenic peptides of the present invention, and still remain within the scope of this disclosure. In addition, amino acids with non-standard R groups (ie, R groups other than the 20 common amino acids of native proteins) can also be used for substitution purposes to produce immunogens and immunogenic polypeptides according to the present invention. If substitutions at more than one position are found to result in peptide antigenic activity substantially equal to or greater than the values defined below, combinations of these substitutions are tested to determine whether the combined substitutions produce additive or synergistic effects on peptide antigenicity. No more than 4 positions within a peptide can be substituted at the same time. The term "T cell response" refers to the specific diffusion and initiation of effector functions induced by a peptide in vitro or in vivo. For MHC class I-restricted CTL, the effector function may be lysis of peptide-pulsed, peptide-precursor-pulsed or native peptide-presenting target cells, secretion of cytokines, preferably peptide-induced interferon-gamma, TNF-alpha or IL -2. Secretion of effector molecules, preferably peptide or degranulation-induced granzymes or perforin. Preferably, when a peptide-specific CTL of any sequence of SEQ ID NOs: 1 to 33 is detected compared to the substituted peptide, the concentration of the peptide does not exceed if the substituted peptide achieves a half-maximal increase in solubility relative to the background peptide About 1 mM, preferably no more than about 1 µM, more preferably no more than about 1 nM, still more preferably no more than about 100 pM, and most preferably no more than about 10 pM. It is also preferred that the substituted peptide is recognized by more than one CTL, at least two, and more preferably three. Therefore, the epitopes described in the present invention may be the same as native tumor-associated epitopes or tumor-specific epitopes, and may also include different peptides of no more than 4 residues from the reference peptide, as long as they have substantially the same antigenic activity i.e. Can. immunotherapy The ability to stimulate an immune response depends on the presence of antigens that are considered foreign by the host immune system. The discovery of tumor-associated antigen presentation raises the possibility of using the host immune system to intervene in tumor growth. For cancer immunotherapy, various mechanisms that control humoral and cellular immunity in the immune system are currently being explored. Certain elements of the cellular immune response specifically recognize and destroy tumor cells. Cytotoxic T-cells (CTL) isolated from tumor-infiltrating cell populations or peripheral blood suggest that these cells play an important role in the innate immune defense of cancer. In particular, CD8-positive T cells play an important role in this response by recognizing major histocompatibility complexes (major histocompatibility complexes) of usually 8 to 12 amino acid residues derived from proteins or from defective ribosomal products (DRIPs) located in the cytoplasm. Class I molecules contained in peptides contained in MHC). Human MHC molecules are also known as human leukocyte-antigens (HLA). MHC class I molecules, which can be found on cells where the nucleus presents peptides resulting from proteolytic cleavage of major endogenous, cytoplasmic or nuclear proteins, DRIPS and larger peptides. However, peptides derived from endosomal structures or from exogenous sources are also frequently found on MHC class I molecules. This non-classical presentation of class I-molecules is referred to in the literature as cross-presentation. Special conditions must be met for proteins to be recognized by cytotoxic T lymphocytes as tumor-specific or associated antigens and for use in therapy. This antigen should be predominantly expressed by tumor cells, whereas normal healthy tissue should not express it at all or to a lesser extent. More suitably, the corresponding antigen is not only present in one tumor, but also in a high concentration (ie, the number of copies of the corresponding peptide per cell). Tumor-specific and tumor-associated antigens are usually derived from proteins that are directly involved in the transformation of normal cells into tumor cells due to functions such as cell cycle regulation or apoptosis. In addition, downstream targets of these proteins that directly lead to transformation may also be up-regulated and thus indirectly associated with tumors. These indirect tumor-associated antigens may also be targets for vaccination approaches. Crucially, in both cases, epitopes of the antigenic amino acid sequence are present, so that such peptides from tumor-associated antigens ("immunogenic peptides") can elicit T cell responses in vitro or in vivo. Basically, any peptide that can bind to an MHC molecule might act as a T-cell epitope. A prerequisite for inducing a T cell response in vitro or in vivo is the presence of T cells with the corresponding TCR and the absence of immune tolerance to that particular epitope. Therefore, TAA is the starting point for the development of tumor vaccines. Methods to identify and characterize TAAs are based on the use of CTLs in patients or healthy subjects, or on the generation of differential transcriptional properties or differential expression patterns between tumor and normal tissue peptides (Lemmel et al. 450-54; Weinschenk et al. 5818-27). However, the identification of genes that are overexpressed or selectively expressed in tumor tissues or human tumor cell lines does not provide accurate information on the antigens transcribed by these genes for use in immunotherapy. This is because T cells with the corresponding TCR must be present and immune tolerance to this particular epitope must be non-existent or minimal, so only a subset of these antigenic epitopes are suitable for this application. Therefore, it is important to select only those peptides that are overexpressed or selectively expressed, and that these peptides are presented in conjunction with MHC molecules that can be found against functional T cells. Such functional T cells are defined as T cells capable of clonally expanding and capable of performing effector functions ("effector T cells") upon stimulation with a specific antigen. Helper T cells play an important role in orchestrating CTL effector functions for antitumor immunity. Trigger T_H1 Cell-responsive helper T cell epitopes support the effector functions of CD8-positive killer T cells, including cytotoxicity directly on tumor cells that display tumor-associated peptide/MHC complexes on their surface. In this way, tumor-associated T helper cell epitopes, alone or in combination with other tumor-associated peptides, can be used as active pharmaceutical ingredients in vaccine compounds that stimulate anti-tumor immune responses. Since CD8 and CD4-dependent responses jointly and synergistically promote antitumor effects, the recognition and identification of tumor-associated antigens by CD8-positive CTLs (MHC-I molecules) or CD4-positive CTLs (MHC-class II molecules) is very important for the development of tumor vaccines. important. Therefore, it is an object of the present invention to propose compositions containing peptides that bind to either class of MHC complexes. Given the severe side effects and costs associated with treating cancer, better prognostic and diagnostic methods are urgently needed. Therefore, it is often necessary to identify other factors that represent biomarkers for cancer, especially gastric cancer. In addition, it is often necessary to identify factors that can be used to treat cancer, especially gastric cancer. In addition, there is no established treatment design for patients with gastric cancer that has biochemically recurred after radical prostatectomy, usually as a result of locally advanced tumor growth from residual tumor at the primary site. There is a need for new treatments that reduce morbidity and are comparable in efficacy to existing treatments. The present invention proposes peptides useful in the treatment of gastric cancer and other tumors that overexpress the peptides of the present invention. These peptides were directly revealed by mass spectrometry and naturally presented by HLA molecules in human primary gastric cancer samples (see Example 1 and Figure 1). The derived peptide-derived gene showed high overexpression in gastric cancer, renal cell carcinoma, colon cancer, non-small cell lung cancer, adenocarcinoma, prostate cancer, benign tumor and malignant melanoma compared to normal tissues (see Example 2 and Figure 2), indicating that these peptides are highly associated with tumors, that is, these peptides are abundantly presented in tumor tissues but not in normal tissues. HLA-binding peptides can be recognized by the immune system, especially T lymphocytes/T cells. T cells can destroy cells presenting recognized HLA/peptide complexes (eg, gastric cancer cells presenting derived peptides). All peptides of the present invention have demonstrated the ability to stimulate T cell responses (see Example 3 and Figure 3). Therefore, these peptides can be used to generate an immune response in a patient, thereby being able to destroy tumor cells. A patient's immune response can be induced by direct administration to the patient of the peptides or precursors (eg, elongated peptides, proteins, or nucleic acids encoding these peptides), ideally in combination with an agent that enhances immunogenicity. The immune response derived from this therapeutic vaccine is expected to be highly specific against tumor cells because the target peptides of the present invention are presented in a low number of copies on normal tissues, preventing patients from developing adverse autoimmune responses against normal cells. risk. The pharmaceutical composition includes the peptide in free form or in a pharmaceutically acceptable salt form. "Pharmaceutically acceptable salt" as used herein refers to a derivative of the disclosed peptide, wherein the peptide is modified with a salt of an antacid or an agent. For example, acid salts take free radicals (usually where the neutral form of the drug has a neutral -NH₂ group) by reaction with a suitable acid. Acids suitable for the preparation of acid salts include organic acids such as: acetic acid, propionic acid, hydroxy acid, pyruvic acid, oxalic acid, malic acid, malonic acid, succinic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzene Formic acid, cinnamic acid, mandelic acid, methanesulfonic acid, methanesulfonic acid, benzenesulfonic acid, salicylic acid, etc., and inorganic acids such as: hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, etc. Conversely, halide salt formulations of acidic groups that can be presented on a peptide are prepared using pharmaceutically acceptable halide groups, such as sodium hydroxide, potassium hydroxide, ammonium hydroxide, calcium hydroxide, trimethylamine, and the like. In particularly preferred embodiments, the pharmaceutical composition includes the peptide in the form of acetic acid (acetate) or hydrochloric acid (chloride). In addition to their use in the treatment of cancer, the peptides of the present invention can also be used in diagnosis. Since the peptide isgastric cancer cells produced, and it has been determined that these peptides are not present in normal tissues, so these peptides can be used to diagnose the presence or absence of cancer. Tissue sections containing the claimed peptides may assist pathologists in diagnosing cancer. Detection of certain peptides using antibodies, mass spectrometry, or other methods known in the art allows the pathologist to determine whether the tissue is malignant, inflammatory, or general. The presentation of peptide groups enables classification or further subclassification of diseased tissue. Detection of peptides in lesion specimens allows for a judgment of interest in a therapeutic approach to the immune system, especially if T-lymphocytes are known or predicted to be involved in the mechanism of action. Loss of MHC expression is a mechanism by which infected malignant cells escape immune surveillance. Thus, the presentation of the peptides indicated that the analyzed cells did not utilize this mechanism. Peptides can be used to analyze lymphocyte responses to peptides (eg, T cell responses), or antibody responses to peptides or peptides complexed with MHC molecules. These lymphocyte responses can be used as prognostic indicators to decide whether to take further treatment. These responses can also be used as surrogate markers in immunotherapy, aiming to induce lymphocyte responses in different ways, such as vaccination with protein, nucleic acids, autologous material, adoptive transfer of lymphocytes. In gene therapy, the response of lymphocytes to peptides can be considered in the assessment of side effects. Lymphocyte response monitoring may also be a valuable tool in follow-up examinations of transplant therapy, eg, for the detection of graft-versus-host and host-versus-graft disease. Peptides can be used to generate and develop specific antibodies against MHC/peptide complexes. These antibodies can be used in therapy, targeting toxins or radioactive substances to diseased tissue. Another use of these antibodies is to target radionuclides to diseased tissue for imaging purposes such as PET. This can help detect small metastases or determine the size and exact location of diseased tissue. In addition, these TUMAPs can be used to validate a pathologist's diagnosis of cancer on the basis of biopsy samples. Table 2 shows the peptides according to the present invention, their respective SEQ ID NOs, and the source proteins from which these peptides may be produced. All peptides bound to the HLA A*024 allele. Table 2: Peptides in the present invention SEQ ID NO: Peptide code sequence source protein 1 CDC2-001 LYQILQGIVF CDK1 2 ASPM-002 SYNPLWLRI ASPM 3 UCHL5-001 NYLPFIMEL UCHL5 4 MET-006 SYIDVLPEF MET 5 PROM1-001 SYIIDPLNL PROM1 6 MMP11-001 VWSDVTPLTF MMP11 7 MST1R-001 NYLLYVSNF MST1R 8 NFYB-001 VYTTSYQQI NFYB 9 SMC4-001 HYKPTPLYF SMC4 10 UQCRB-001 YYNAAGFNKL UQCRB 11 PPAP2C-001 AYLVYTDRL PPAP2C 12 AVL9-001 FYISPVNKL AVL9 13 NUF2-001 VYGIRLEHF NUF2 14 ABL1-001 TYGNLLDYL ABL1 15 MUC6-001 NYEETFHI MUC6 16 ASPM-001 RYLWATVTI ASPM 17 EPHA2-005 VYFSKSEQL EPHA2 18 MMP3-001 VFIFKGNQF MMP3 19 NUF2-002 RFLSGIINF NUF2 20 PLK4-001 QYASRFVQL PLK4 twenty one ATAD2-002 KYLTVKDYL ATAD2 twenty two COL12A1-001 VYNPTPNSL COL12A1 twenty three COL6A3-001 SYLQAANAL COL6A3 twenty four FANCI-001 FYQPKIQQF FANCI 25 RPS11-001 YYKNIGLGF RPS11 26 ATAD2-001 AYAIIKEEL ATAD2 27 ATAD2-003 LYPEVFEKF ATAD2 28 HSP90B1-001 KYNDTFWKEF HSP90B1 29 SIAH2-001 VFDTAIAHLF SIAH2 30 SLC6A6-001 VYPNWAIGL SLC6A6 31 IQGAP3-001 VYKVVGNLL IQGAP3 32 ERBB3-001 VYIEKNDKL ERBB3 33 KIF2C-001 IYNGKLFDLL KIF2C Other HLA A*02 peptides of interest in the present invention: SEQ ID NO: Peptide code sequence source protein 34 CCDC88A-001 QYIDKLNEL CCDC88A 35 CCNB1-003 MYMTVSIIDRF CCNB1 36 CCND2-001 RYLPQCSYF CCND2 37 CCNE2-001 IYAPKLQEF CCNE2 38 CEA-010 IYPDASLLI CEACAM1, CEACAM5, CEACAM6 39 CLCN3-001 VYLLNSTTL CLCN3 40 DNAJC10-001 IYLEVIHNL DNAJC10 41 DNAJC10-002 AYPTVKFYF 42 EIF2S3-001 IFSKVSLF EIF2S3, LOC255308 43 EIF3L-001 YYYVGFAYL EIF3L, LOC340947 44 EPPK1-001 RYLEGTSCI EPPK1 45 ERBB2-001 TYLPTNASLSF ERBB2 46 GPR39-001 SYATLLHVL GPR39 47 ITGB4-001 DYTIGFGKF ITGB4 48 LCN2-001 SYNVTSVLF LCN2 49 SDHC-001 SYLELVKSL LOC642502, SDHC 50 PBK-001 SYQKVIELF PBK 51 POLD3-001 LYLENIDEF POLD3 52 PSMD14-001 VYISSLALL PSMD14 53 PTK2-001 RYLPKGFLNQF PTK2 54 RPS11-001 YYKNIGLGF RPS11 55 TSPAN1-002 VYTTMAEHF TSPAN1 56 ZNF598-001 DYAYLREHF ZNF598 57 ADAM10-001 LYIQTDHLFF ADAM10 58 MMP12-001 TYKYVDINTF MMP12 59 RRM2-001 YFISHVLAF RRM2 60 TMPRSS4-001 VYTKVSAYL TMPRSS4 61 TSPAN8-001 VYKETCISF TSPAN8 In another embodiment of the present invention, an HLA A*02 binding peptide against gastric cancer is disclosed. For A*02 and/or A*24 positive people, the disclosed mixture of peptides can be used to treat gastric cancer. Preferred are mixtures of 2 to 20 peptides and 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 and 20 peptides of the mixture. SEQ ID NO: Peptide code sequence source protein 62 DIO2-001 ALYDSVILL DIO2 63 IGF2BP3-001 KIQEILTQV IGF2BP3 64 LMNB1-001 LADETLLKV LMNB1 65 WNT5A-001 AMSSKFFLV WNT5A 66 FAP-003 YVYQNNIYL FAP 67 COPG-001 VLEDLEVTV COPG, COPG2, TSGA13 68 COL6A3-002 FLLDGSANV COL6A3 69 COL6A3-003 NLLDLDYEL COL6A3 70 COL6A3-004 FLIDSSEGV COL6A3 71 PSMC2-001 ALDEGDIAL PSMC2 72 UBE2S-001 ALNEEAGRLLL UBE2S 73 KIF11-001 ILSPTVVSI KIF11 74 ADAM8-001 KLLTEVHAA ADAM8 75 CCNB1-001 ALVQDLAKA CCNB1 76 CDC6-001 ILQDRLNQV CDC6 77 F2R-001 TLDPRSFLL F2R 78 OLFM4-001 TLDDLLLYI OLFM4 79 THY1-001 SLLAQNTSWLL THY1 80 CEP250-001 SLAEVNTQL CEP250 81 HIF1A-001 ALDGFVMVL HIF1A 82 KRAS-001 GVDDAFYTL KRAS 83 MET-001 YVDPVITSI MET 84 NCAPG-001 YLLSYIQSI NCAPG 85 NCAPG-002 QIDDVTIKI NCAPG 86 TOP-004 YLYGQTTTYL TOP2A 87 TOP-005 KLDETGNSL TOP2A 88 LAMC2-002 RLDDLKMTV LAMC2 89 AHR-001 LTDEILTYV AHR 90 CCNB1-002 ILIDWLVQV CCNB1 91 CEACAM6-001 VLYGPDVPTI CEACAM6 92 COPB1-001 SIFGEDALANV COPB1 93 HMMR-001 KLLEYIEEI HMMR 94 TPX2-001 KILEDVVGV TPX2 95 TOP-001 KIFDEILVNA TOP2A, TOP2B cell division cycle 2 protein (CDC2) The serine/threonine kinase CDC2, also known as Cdk1 (Cyclin-Dependent Kinase 1), plays a key role in cell cycle control. It is known to be a major regulator of the G2 to M transition. At the end of interphase, it binds to A-type cyclins. After nuclear envelope rupture, type A cyclins are replaced by cyclin B, which together with Cdc2 forms a mitosis-promoting factor (MPF). MPF is essential for driving cells to complete mitosis. The function of Cdc2 in mitosis is not redundant and cannot be compensated by the activity of other Cdk such as Cdk2, Cdk4 and Cdk6. Conversely, it has also been reported that Cdc2 plays a role in other phases of the cell cycle, such as the G1-S transition, and that it can replace "interphase Cdk". Therefore, Cdc2 is considered to be the only essential cell cycle Cdk. Overexpression of Cdc2 is often associated with poor prognosis in several cancers. Such cancers are prostate cancer, oral cancer, oral squamous cell carcinoma (OSCC), acute myeloid leukemia (AML) (Qian et al.), MALT lymphoma caused by H. pylori (Banerjee et al., 217-25 ) and colon cancer (Yasui et al., 36-41). In gastric cancer, overexpression and/or enhanced activity have been reported and may play a pathogenic role. Inhibitors of Cdc2 and other Cdk have also been considered as candidates for cancer therapy (Shapiro 1770-83).abnormal spindle microcephaly associated protein (ASPM) Abnormal spindle microcephaly-associated protein (ASPM) is the human ortholog of Drosophila abnormal spindle (asp), which is involved in the regulation of neurogenesis and whose mutation causes somatic recessive primary microcephaly. ASPMs are located at the spindle poles during mitosis. Overexpression of ASPM has been suggested as a marker of glioblastoma and a potential therapeutic target. siRNA-mediated blockade of gene expression can inhibit tumor cell proliferation and neural stem cell proliferation. Overexpression of ASPM also predicts increased invasiveness/metastatic potential, early tumor recurrence, and poor prognosis in HCC. ASPM is upregulated in immortalized cells and non-small cell lung cancer tissues (Jung, Choi, and Kim 703-13).matrix metalloproteinase 3 (MMP3) MMP3, also known as progelatinase or stromelysin 1, is responsible for the degradation of extracellular matrix (ECM) components such as fibronectin, laminin, elastin, proteoglycan core protein, and collagen non-helical regions Endopeptidase. MMPs are important for several physiological processes that require ECM rearrangement, such as embryonic development, tissue remodeling, vascularization, mammalian mammary gland involution, and cell migration during wound healing. MMP3 also plays a role in platelet aggregation. Pathological conditions involving enhanced expression and secretion of MMP3 include autoimmune inflammatory conditions and cancer. MMP3 is overexpressed in some tumors and plays a role in epithelial-mesenchymal transition (EMT). It may also be involved in the early steps of carcinogenesis, triggering extragenic changes leading to malignant phenotypes (Lochter et al., 180-93). Polymorphisms in the MMP3 promoter associated with expression levels have been shown to influence risk and prognosis in certain cancers, such as esophageal adenocarcinoma (Bradbury et al., 793-98) and oral squamous cell carcinoma (Vairaktaris et al., 4095 -100) (Liu et al., 430-35). Helicobacter pylori-positive gastric cancer patients with elevated serum levels of MMP3 and MMP7 showed higher lymph node invasion and shorter survival. In a cohort of 74 gastric cancer patients, 27% had MMP3 expression (Murray et al., 791-97).c-Met c-Met mediates the potential oncogenic activities of hepatocyte growth factor (HGF)/scatter factor, including promotion of cell growth, motility, survival, extracellular matrix lysis and angiogenesis. Binding of HGF activates downstream signaling events, including Ras, phosphatidylinositol 3'-kinase, phospholipase Cγ, and mitogen-activated protein kinase-related pathways (Dong et al., 5911-18; Furge et al., 10722-27 Furge, Zhang, and Vande Woude 5582-89; Montesano et al., 355-65; Naldini et al., 501-04; Ponzetto et al., 4600-08). c-Met is mainly expressed in epithelial cells. Oncogenic activation of c-Met (also in non-epithelial malignant tissues) can result from amplification/overexpression, activating mutation, acquisition of the HGF/c-Met autocrine loop, or constitutive phosphorylation (Di Renzo et al., 147- 54; Ferracini et al., 739-49; Fischer et al., 733-39; Koochekpour et al., 5391-98; Li et al., 8125-35; Maulik et al., 41-59; Qian et al., 589-96; Ramirez et al, 635-44; Tuck et al, 225-32) (Nakaigawa et al, 3699-705). Constitutive activation of c-Met in HGF-overexpressing transgenic mice promotes extensive tumor formation (Takayama et al., 701-06; Wang et al., 1023-34). MET silencing inhibits tumor growth and metastasis (Corso et al., 684-93). Amplification of MET is associated with progression of human gastric cancer (Lin et al., 5680-89) (Yokozaki, Yasui, and Tahara 49-95).ubiquitin carboxy-terminal hydrolase L5(UCHL5) UCHL5, also known as ubiquitin C-terminal hydrolase (UCH37) or INO80R, is a proteasome-associated deubiquitinase. It separates the protein-linked polyubiquitin chain from the distal end by cleaving the isopeptide bond between the C-terminal Cys76 and Lys48 (Nishio et al., 855-60). In the nucleus, UCHL5 associates with the Ino80 chromatin remodeling complex. Upon binding to the proteasome, it is activated and may be involved in transcriptional regulation or DNA repair, which is suggested to be mediated by Ino80 and the proteasome. Ubiquitin-specific proteases such as UCHL5 are involved in several processes such as control of cell cycle progression, differentiation, DNA replication and repair, transcription, protein quality control, immune responses and apoptosis. UCHL5 may promote malignant transformation. Its activity has been shown to be up-regulated in human cervical cancer tissue compared to adjacent normal tissue. It is capable of deubiquitination, thereby stabilizing the TGF-beta receptor and its downstream regulator Smad, and thereby enhancing TGF-beta signaling. Although TGF-β signaling has dual functions and can also act as a tumor suppressor in early and precancerous stages of cancer, enhanced TGF-β signaling can act as a tumor promoter in late stages of cancer progression (Bierie and Moses 29-40; Horton et al., 138-43; Wicks et al, 8080-84; Wicks et al, 761-63).macrophage stimulating protein receptor (MST1R) The MST1R (alias RON) receptor is a member of the Met family of cell surface receptor tyrosine kinases and is mainly expressed on epithelial cells and macrophages. MST1R can induce cell migration, invasion, proliferation and survival in response to its ligands. Its oncogenic properties have been shown in vitro and in animal models, and are often downregulated in human cancers (Dussault and Bellon, 2009). Clinical studies have shown that overexpression of MST1R is associated with poor prognosis and metastasis. MST1R is significantly expressed in gastric cancer tissues and corresponding paraneoplastic tissues, but not in normal gastric mucosa (Zhou et al., 236-40). Blockade of MST1R expression in prostate cancer cells results in reduced endothelial chemotaxis in vitro and reduced tumor growth and microvessel density after orthotopic transplantation into the prostate in vivo. In highly tumorigenic colon cancer cell lines, siRNA-mediated blockade of MST1R expression resulted in decreased proliferation compared to control cells.kinesin-like protein (KIF2C) KIF2C is a microtubule depolymerase that regulates proper kinetochore-microtubule junctions during spindle formation. It is important for anaphase chromosome segregation and may be required to coordinate sister centromere segregation. Disruption of microtubule junctions at the kinetochore has been observed to result in chromosomal missegregation and aneuploidy in most solid tumors (Maney et al., 67-131; Moore and Wordeman 537-46). KIF2C is overexpressed in breast cancer cells (Shimo et al., 62-70), colon cancer, colorectal cancer and gastric cancer (Nakamura et al., 543-49). The gastric cancer cell line (AZ521) stably expressing KIF2C showed increased proliferation and metastasis compared to mock-transfected cells. The elevated expression of KIF2C in gastric cancer may be associated with lymphatic invasion, lymph node metastasis and poor prognosis. Treatment of breast cancer cells with small interfering RNA against KIF2C inhibits breast cancer cell growth.Chromosome structure maintenance protein 4 (SMC4) SMC proteins are chromosomal ATPases that play a role in high-level chromosome organization and dynamics. SMC4 is a core component of the condensin complex, which plays a role in chromatin condensation and is also involved in nucleolar segregation, DNA repair and maintenance of the chromatin scaffold. It is known that the SMC4 gene is highly expressed in normal prostate and salivary glands, extremely weakly expressed in colon, pancreas and intestine, and not expressed at all in other tissues. High RNA expression levels have been observed in many cancer cell lines and cancer samples, including breast, prostate, colon and pancreatic cancers (Egland et al., 5929-34).Ephrin A type receptor 2(EPAH2) Eph receptors are a unique family of receptor tyrosine kinases (RTKs) that play critical roles in embryonic patterning, neuronal targeting, and vascular development during normal embryogenesis. Stimulation of EphA2 with its ligand (ephrin-A1) results in EphA2 autophosphorylation, which reverses the oncogenic transformation. Eph receptors and their ligands, ephrin, are frequently overexpressed in a variety of cancers. EphA2 is frequently overexpressed and functionally altered in aggressive tumor cells, and is thought to promote tumor growth by enhancing cell-extracellular matrix adhesion, anchorage-dependent growth, and angiogenesis. Excessive expression of EphA2 and EphrinA-1 is shown in gastric cancer, which correlates with the depth of tumor invasion, tumor lymph node metastasis (TNM) stage, lymph node metastasis and poor prognosis (Yuan et al., 2410-17).ATAD2 ATAD2 (also known as ANCCA) is a new member of the AAA+ ATPase family of proteins. It enhances the transcriptional activity of androgen receptor (AR) and estrogen receptor (ER), which induces proteins including IGF1R, IRS-2, SGK1 and survivin (AR) and cyclins D1, c-myc and E2F1 (ER), respectively. ) gene transcription. It also enhances the transcriptional activity of c-Myc. ATAD2 expression is higher in several human tumors such as breast cancer, prostate cancer and osteosarcoma. Its manifestations are associated with poor prognosis.AVL9 This protein was unexpectedly found to be the source protein, and there is little and very limited data on the function of the AVL9 protein and corresponding genes.Collagen α-1(XII) catenin (Col12A1) Collagen alpha-1 (XII) chain is a protein that is encoded in humans by the COL12A1 gene. This gene encodes the alpha chain of collagen type XII, which is a member of the FACIT (fibril-associated collagen of discontinuous triple helix) collagen family. Type XII collagen is found to bind to type I collagen as a homotrimer, and this binding is thought to modify the interaction between collagen I fibrils and the surrounding matrix. Alternative splice transcript variants that encode different isoforms have been identified.Collagen α-3(VI) catenin (COL6A3) COL6A3 encodes the alpha-3 chain, one of the three alpha chains of type VI collagen. This protein domain has been shown to bind to extracellular matrix proteins, an interaction that illustrates the importance of this collagen in tissue matrix components. In ovarian cancer cells, remodeling of the extracellular matrix via overexpression of collagen VI contributes to cisplatin resistance. The presence of collagen VI correlates with tumor grade, which is a prognostic factor for ovarian cancer (Sherman-Baust et al., 377-86). COL6A3 is overexpressed in colorectal tumors (Smith et al, 1452-64), salivary gland carcinomas (Leivo et al, 104-13) and differentially expressed in gastric cancer (Yang et al, 1033-40). COL6A3 has been identified as one of seven genes with tumor-specific splice variants. The demonstrated tumor-specific splicing changes are highly concordant, thus enabling a clear distinction between normal and cancer samples, and in some cases even between different tumor stages (Thorsen et al., 1214-24).Fanconi (Fanconi) Anemia complementation group I(FANCI) FANCI proteins localize to chromatin in response to DNA damage and are involved in DNA repair (Smogorzewska et al., 289-301). Mutations in the FANCI gene cause Fanconi anemia, a recessively genetically heterogeneous disorder characterized by cytogenetic instability, hypersensitivity to DNA cross-linking agents, increased chromosomal breaks, and defects in DNA repair. Alternative splicing of FANCI forms two transcript variants encoding different isoforms.heat shock protein 90 kDaβ member 1(HSP90B1) HSP90 (also known as glucose-regulated protein 94, Grp94) member 1 is a human chaperone protein. It is involved in ER-related processes: translation, protein quality control and ER-related degradation (ERAD), ER stress sensing and calcium binding/retention in the ER (Christianson et al., 272-82; Fu and Lee 741-44). HSP90 contains the KDEL sequence typical of ER-retained proteins, but it is also present on the surface of tumor cells (Altmeyer et al., 340-49) and extracellularly. HSPs are known to be released from necrotic (rather than apoptotic) cells and cells stressed by various stimuli, such as heat shock and oxidative stress, and can appear in the circulation (Basu et al., 1539-46; Tsan and Gao 274 -79). Extracellularly, HSP90 regulates (mainly stimulates) immune responses and is involved in antigen presentation. On the cell surface, it can act as a receptor for pathogen entry and/or signaling (Cabanes et al., 2827-38). In the case of tumor-specific cell surface expression or release, it can induce anti-tumor immunity (Zheng et al., 6731-35). In both prophylactic and therapeutic regimens, HSP90-based vaccines have shown immunity against cancer and infectious diseases (reviewed in (Bolhassani and Rafati 1185-99; Castelli et al., 227-33; Murshid, Gong, and Calderwood 1019). -30) in). However, HSP90 may also be considered a target for tumor therapy because 1) it is associated with tumor progression and also elicits resistance to apoptosis after irradiation or chemotherapy treatment; and 2) it is overexpressed in many tumors, including GC, osteosarcoma (Guo et al, 62-67), breast cancer (Hodorova et al, 31-35). Overexpression of HSP90 is associated with aggressive behavior and poor prognosis in GC (Wang, Wang, and Ying 35-41; Zheng et al., 1042-49). Downregulation of HSP90 in GC induces apoptosis in cancer cells (Sheu, Liu, and Lan e1096).Muc 6 MUC6 is expressed in mucous cells. Its primary function is believed to lie in protecting vulnerable epithelial surfaces from the damaging effects of constant exposure to various endogenous caustic or proteolytic agents (Toribara et al., 1997). MUC6 also plays a role in epithelial organogenesis (Reid and Harris, 1999). MUC6 was found to be expressed in normal gastric mucosa. It is overexpressed in some cancers, such as intestinal adenomas and carcinomas of the bowel, lung (Hamamoto et al, 891-96), colorectal polyps (Bartman et al, 210-18) and breast cancer (Pereira et al, 210-13) , but not in the respective normal tissues. Due to its high rate of expression in mucinous carcinomas, MUC6 has been suggested to act as a barrier to the spread of cancer, resulting in a less aggressive biological behavior (Matsukita et al., 26-36). The expression of MUC6 in gastric cancer was lower than that in adenoma or normal mucosa, and was negatively correlated with tumor size, depth of invasion, lymphatic and venous invasion, lymph node metastasis and UICC stage. Downregulation of MUC6 promotes malignant transformation of gastric epithelial cells and underlies the molecular basis of gastric cancer growth, invasion, metastasis and differentiation (Zheng et al., 817-23). There is also evidence that H. pylori infection, a major cause of gastric cancer, is associated with reduced MUC6 expression (Kang et al., 29-35; Wang and Fang 425-31).kinetochore protein Nuf2 The NUF2 (CDCA-1) gene encodes a protein highly similar to yeast Nuf2, which is a component of a conserved protein complex associated with centromeres. In prophase meiosis, when the centromere is disconnected from the spindle pole body, yeast Nuf2 autonomically disappears from the centromere and plays a regulatory role in chromosome segregation. Studies have shown that survivin and hNuf2 csiRNA temporarily block its mRNA expression and cause multinucleation and cell death, respectively, by blocking mitosis (Nguyen et al., 394-403). Nuf2 and Hec1 are required for stable microtubule plus-end binding site organization in the outer plate, which is required for the sustained polar force required for biaxial orientation at the kinetochore (DeLuca et al., 519-31). Nuf2 protein was found to be overexpressed in NSCLC (associated with poor prognosis) (Hayama et al., 10339-48) and cervical cancer (Martin et al., 333-59). In surgically resected gastric cancer tissues (diffuse type, 6; intestinal type, 4), two NUF2 variants were up-regulated. Alternative splice variants detected in this study were suggested to be potentially useful as diagnostic markers and/or novel targets for anticancer therapy (Ohnuma et al., 57-68). siRNA-mediated blockade of expression of NUF2 was found to inhibit cell proliferation and induce apoptosis in NSCLC, ovarian, cervical, gastric, colorectal, and gliomas (Kaneko et al., 1235-40) .lipid phosphate phosphohydrolase 2(PPAP2C) Phosphatidic acid phosphatase (PAP) converts phosphatidic acid to diacylglycerol and plays a role in glycerolipid de novo synthesis and in phospholipase D-mediated receptor activation signaling. It has been reported to have three alternative spliced transcript variants encoding different isoforms. PPAP2C is upregulated in transformed primary adult mesenchymal stem cells (MSCs) and many human cancers. It may be required for increased cell proliferation. Overexpression of PPAP2C (but not the catalytically inactive mutant) results in premature entry into S phase with precocious cyclin A accumulation. Blocking its gene expression can reduce cell proliferation by delaying entry into S phase (Flanagan et al., 249-60).40S ribosomal protein S11 for a protein (RPS11) The ribose system consists of a small 40S subunit and a large 60S subunit. In total, these subunits consist of 4 RNAs and about 80 structurally distinct proteins. The RPS11 gene encodes a ribosomal protein that is a component of the 40S subunit. RPS11 is one of six genes that have been found to be useful for screening stool RNA-based markers for the diagnosis of colorectal cancer. It is especially found in fecal colon cells derived from cancer patients (Yajima et al., 1029-37).E3 Ubiquitin protein ligase seven deletion (absentia) homologue 2(SIAH2) SIAH2 is an E3 ubiquitin ligase. Its substrates are β-catenin, TRAF2 and DCC (deleted in colorectal cancer) (Habelhah et al., 5756-65; Hu and Fearon 724-32; Nakayama, Qi, and Ronai 443-51). SIAH2 also leads to the degradation of the nuclear protein repp86, thereby causing the elimination of the mitotic arrest induced by overexpression of this protein (Szczepanowski et al., 485-90). SIAH2 has tumor- and metastasis-promoting properties via at least two pathways (see Nakayama, Qi, and Ronai 443-51): first, it causes ubiquitination and degradation of proteins in the hypoxia-responsive pathway, thereby enhancing hypoxia Transcriptional activity of inducible factor (HIF) (Nakayama, Qi, and Ronai 443-51) (Calzado et al., 85-91). Second, it inhibits Sprouty2, a specific inhibitor of Ras/ERK signaling. SIAH2 activity may be associated with the development of pancreatic tumors through its positive effect on Ras signaling (Nakayama, Qi, and Ronai 443-51). Although the role of SIAH2 in cancer is partially debated, some reports suggest that low levels of SIAH2 are associated with poor prognosis or treatment response (Confalonieri et al., 2959-68) (Jansen et al., 263-71), and other reports suggest that it has Oncogenic function (Frasor et al., 13153-57). SIAH2 inhibition has been considered as an anticancer therapy because it has been shown to inhibit xenograft growth in mouse models of melanoma (Qi et al., 16713-18; Shah et al., 799-808) and to inhibit transplantation into nude mice. Growth of human lung cancer cell lines in mice (Ahmed et al., 1606-29).Sodium and Chlorine Dependent Taurine Transporter (SLC6A6) SLC6A6 is a sodium and chloride dependent taurine transporter (TauT) (Han et al., 2006). Taurine transporter knockout (taut-/-) mice develop chronic liver disease due to taurine deficiency, which may involve mitochondrial dysfunction (Warskulat et al., 2006). The expression of SLC6A6 is repressed by the p53 tumor suppressor gene and inactivated by proto-oncogenes such as WT1, c-Jun and c-Myb. Overexpression of SLC6A6 protects renal cells from cisplatin-induced nephrotoxicity (Han et al., 2006; Han and Chesney, 2009). In human intestinal epithelial Caco-2 cells, the mRNA expression of SLC6A6 is up-regulated by tumor necrosis factor alpha (TNF-alpha).panthenol - Cytochrome c reductase binding protein (UQCRB) The protein encoded by the UQCRB gene is part of the ubiquinol-cytochrome c oxidoreductase complex. It binds to ubiquinone and participates in electron transport. Mutations in this gene are associated with mitochondrial complex III deficiency. Pseudogenes on the X chromosome have been documented. The UQCRB gene may be a potential oncogene or tumor suppressor gene in pancreatic ductal adenocarcinoma (Harada et al., 13-24). It has been found to be overexpressed in hepatocellular carcinoma (Jia et al., 1133-39).human epidermal growth factor receptor 3(ERBB3) ERBB3 encodes a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. It is activated by neuregulin, other ERBB and non-ERBB receptors, and other kinases, and is activated by a novel mechanism. Downstream, it interacts primarily with the phosphoinositide 3-kinase/AKT survival/mitogenic pathway, and also with GRB, SHC, SRC, ABL, rasGAP, SYK, and the transcriptional regulator EBP1 (Sithanandam and Anderson 413-48 ). Overexpression of ERBB3 has been found in many cancers, including gastric cancer, where it may play a key pathogenic role and negatively impact prognosis (Kobayashi et al., 1294-301) (Slesak et al., 2727-32). (Zhang et al., 2112-18) found that ERBB3 overexpression was more frequent in diffuse-type gastric cancer (26.2%) than in intestinal-type gastric cancer (5.0%). In both types, excess manifestations were associated with poor prognosis. Approaches to targeting ERBB3 in cancer therapy include RNA aptamers targeting the extracellular domain (Chen et al., 9226-31), the use of synthetic transcription factors to block its gene expression (Lund et al., 9082-91), isoforms such as vitamin E Small molecule inhibitors of conformal gamma-tocotriene (Samant and Sylvester 563-74), miRNAs (Scott et al., 1479-86) and siRNAs (Sithanandam et al., 1847-59).Prominin 1 (Prom1) Function: Prominin-1, also known as CD133, was identified as a molecule specific for CD34+ hematopoietic progenitor cells (Yin et al., 1997) and has been shown to be a marker for normal and cancer stem cells (CSCs) in various tissues. It is mainly located in the prominence of the plasma membrane and may be involved in the organization of membrane topology or in maintaining the lipid composition of the plasma membrane. The splice isoform of prominin-1, known as AC133-2 and lacking a small exon of 27 amino acids, is thought to represent a better stem cell marker (Mizrak et al., 2008; Bidlingmaier et al., 2008). Only a small percentage of tumor cells were generally positive for prominin-1, as might be expected for a CSC marker. Depending on the tumor type, the number of positive cells per tumor mass ranges from 1% to 15%, and most are around 2%. Prominin-1 is associated with tumor formation, angiogenesis and chemoresistance (Zhu et al., 2009a) (Bruno et al., 2006; Hilbe et al., 2004) (Bertolini et al., 2009). However, since prominin-1 positive cells may be killed by NK cells (Castriconi et al., 2007; Pietra et al., 2009) and cytotoxic T cells (Brown et al., 2009), they may be invaded by the immune system. Although prominin-1-positive cells have been demonstrated to function as CSCs in many cancer entities, and their performance is often associated with poor prognosis, it remains controversial. Some reports indicate that it is not necessarily or sufficient to determine CSC (Cheng et al., 2009; Wu and Wu, 2009). Perhaps the combination of prominin-1 with other molecules such as CD44, or even multiple combinations such as prom1(+), CD34(+), CD44(+), CD38(-), CD24(-) could serve as a better CSC marker (Zhu et al., 2009b; Fulda and Pervaiz, 2010). In diffuse-type GC, PROM1 expression was presumed based on electron hybridization analysis (Katoh and Katoh, 2007), and (Smith et al., 2008) reported overrepresentation in GC compared to normal gastric tissue protein content. However, (Boegl and Prinz, 2009) reported that prominin-1 expression was decreased in GC, especially at later stages, and argued that prominin-1 expression was associated with angiogenesis (also decreased at later stages), independent of tumor growth. A study using GC cell lines (Takaishi et al., 2009) identified CD44 as a CSC marker for GC, whereas prominin-1 was not.matrix metalloproteinase 11 (MMP11) Like other MMPs, MMP11 is also an endopeptidase that plays a role in processes requiring tissue remodeling, such as development, wound healing, and scarring. It can also negatively regulate adipose homeostasis by reducing adipocyte differentiation. In contrast to other MMPs, it cannot cleave typical extracellular matrix molecules other than collagen VI. However, other receptors for MMP11 have been identified, such as α2-macroglobulin, certain serpins (including α1 antitrypsin), insulin-like growth factor binding protein 1, and laminin receptors . In cancer, MMP11 is mainly expressed in stromal cells surrounding tumor tissue. It has been demonstrated in many tumor entities. MMP11 is thought to be overexpressed in the stroma of most aggressive human cancers, but rarely in sarcomas and other non-epithelial tumors. In most, but not all cases, MMP11 was expressed in stromal cells immediately adjacent to the tumor, and was negative on tumor cells themselves, normal tissue, and stromal cells distant from the tumor. Higher MMP11 levels were associated with malignant phenotype/higher aggressiveness and poor prognosis. However, in papillary thyroid carcinoma, MMP11 expression was negatively correlated with aggressive features. MMP11 was found in tumor tissue as well as in the serum of gastric cancer patients, and its expression correlated with metastasis (Yang et al.). In addition, (Deng et al., 274-81) studies have shown that MMP11 is highly expressed in gastric cancer tumor cell lines and primary tumors, not only in the stroma and in contrast to other cancer types, but also in Seems to enhance tumor cell proliferation.nuclear transcription factor Y subunit β(NFYB) NFYB, also known as CBF-B or CBF-A, is part of the heterotrimeric basal transcription factor NF-Y (also known as CCAAT binding factor or CBF) in addition to NFYA and NFYC, which is associated with many The CCAAT motif (or the reverse motif ATTGG known as the Y-box) in gene promoters and enhancers binds. NF-Y target genes include MHC class II genes, PDGFβ receptor, several heat shock proteins, mismatch repair gene hMLH1 and topoisomerase IIα. NFYB is not a traditional oncogene, however its function may promote tumorigenesis. First, many cell cycle genes such as cyclin A, cyclin B1, aurora kinase A, and cdk1 are targets of NF-Y. Cell arrest in G2/M phase does not require functional NFYB. (Park et al.) showed that up-regulation of cyclin B2 and other cell cycle-related genes in colorectal adenocarcinoma was caused by the activity of NF-Y. Second, the activity of NF-Y hinders apoptosis. Cells lacking NF-Y undergo apoptosis due to p53 activation and decreased transcription of anti-apoptotic genes such as Bcl-2 containing the CCAAT box in the promoter (Benatti et al., 1415-28). Third, its tumorigenicity is enhanced when combined with other transcription factors. For example, binding of mutated p53 to NF-Y and p300 proteins can increase the expression of NF-Y-induced cell cycle genes.ABL1 The protein tyrosine kinase c-Abl shuttles between the nuclear and cytoplasmic compartments. Nuclear c-Abl is involved in cell growth inhibition and apoptosis, while cytoplasmic c-Abl may be involved in actin dynamics, morphogenesis, and signaling induced by extracellular stimuli such as growth factors and integrin ligands Play a role. Cytoplasmic c-Abl has been reported to promote mitosis. The activity of the c-Abl protein is negatively regulated through its SH3 domain, and loss of the SH3 domain renders ABL1 an oncogene. In chronic myeloid leukemia (CML), this gene is activated by translocation within the BCR (Breakpoint Cluster Region) on chromosome 22. The resulting fusion protein, BCR-ABL, is localized in the cytosol and allows cells to proliferate independent of cytokine regulation (Zhao et al.). c-Abl activity is also up-regulated in solid tumors, such as breast and NSCLC. Overexpression is not sufficient and protein phosphorylation is required for constitutive kinase activity. In breast cancer cells, c-Abl phosphorylation is induced by cytoplasmic membrane tyrosine kinases including SFK, EGFR family members and the IGF-1 receptor. ABL fusion proteins have not been detected in solid tumors (Lin and Arlinghaus, 2008). ABL was shown to be expressed in gastric cancer and associated with microvessels, suggesting that it may play a role in angiogenesis. Notably, the H. pylori cytotoxin-associated gene A (CagA) activates c-Abl, thereby phosphorylating EGFR, thereby blocking EGFR endocytosis (Bauer, Bartfeld, and Meyer 156-69). Several tyrosine kinase inhibitors are specific to Abl to some extent. Imatinib (Gleevec) is used as first-line therapy in CML and because it also targets KIT, it is also licensed for advanced gastrointestinal stromal tumor (GIST) patients (Pytel et al., 66-76) (Croom and Perry, 2003). Other inhibitors used in cancer therapy are Dasatinib and Nilotinib (Pytel et al., 66-76) (Deremer, Ustun, and Natarajan 1956-75).Polo like kinase 4 (Plk4) Members of the Polo kinase family (Plk1 to Plk4) are very important during cell division, regulating several steps in the mitotic process. Plk4 is an organizer of centrosome formation and replication (Rodrigues-Martins et al., 1046-50). Although Plk1 is a well-defined oncogene, the function of Plk4 in cancer is not well understood. Downregulation and overexpression of Plk4 is associated with cancer in humans, mice and flies (Cunha-Ferreira et al., 43-49). For example, in colorectal cancer, Plk4 was found to be overexpressed, but a small subset of patients showed strong Plk4 downregulation (Macmillan et al., 729-40). This phenomenon can be explained by the fact that both overexpression and deficiency of Plk4 lead to abnormal centrosome formation and thus to abnormal centrosome number and structure, which are often detected in tumor cells and promote mitosis Aberrations, causing chromosomal misalignment and aneuploidy (Peel et al., 834-43). (Kuriyama et al., 2014-23). (Korzeniewski et al., 6668-75).contains IQ of primitives GTP enzyme-activated protein 3(IQGAP3) IQGAP is involved in cell signaling pathways as well as cytoskeletal structure and cell adhesion. It has a domain with a sequence similar to RasGAP, so it can bind to small GTPases. However, despite their name, none of them have GTPase activating activity. For IQGAP1 and IQGAP2, it has even been shown to stabilize the GTP-bound state of Racl and Cdc42, and IQGAP3 has been shown to stabilize activated Ras (Nojima et al., 971-78; White, Brown, and Sacks 1817-24). It binds to calcium/calmodulin via its IQ domain and to actin filaments via the calmodulin homology domain (White, Brown, and Sacks 1817-24). (Wang et al., 567-77) studies indicate that IQGAP3 is expressed in the brain where it binds wit actin filaments as well as Rac1 and Cdc42. It accumulates in distal regions of axons and promotes Rac1/Ccd42-dependent axonal growth. IQGAP is associated with cancer. IQGAP1 is considered an oncogene. It enhances several cancer-related pathways, such as MAP kinase, beta-catenin, and VEGF-mediated signaling, and is overexpressed in many tumors. IQGAP2 appears to function as a tumor suppressor and was found to be reduced in gastric cancer with poor prognosis (White, Brown, and Sacks 1817-24). Very little information is available about IQGAP3. (Skawran et al., 505-16) found it to be one of the genes significantly up-regulated in hepatocellular carcinoma. Two studies indicated that IQGAP3 is specifically expressed in (Ki67+) cells proliferating in mouse small intestine, colon and liver (Nojima et al., 971-78) (Kunimoto et al., 621-31).coiled-coil domain 88a (CCDC88A) CCDC88A is an actin-bound Akt substrate that plays a role in actin organization and Akt-dependent cellular motility in fibroblasts. The CCDC88A/Akt pathway is also essential in VEGF-mediated post-neovascularization. CCDC88A is also highly expressed in a variety of human malignant tissues, including breast, colon, lung and cervical cancer. It plays an important role in tumor progression accompanied by aberrant activation of the Akt signaling pathway.Cyclin B1(CCNB1) CCNB1 is induced in the G2/M phase of mitosis and forms a mitogenic factor (MPF) together with cyclin-dependent kinase 1 (Cdk1)/Cdc2. It has been found to be overrepresented in a variety of cancers and is often associated with poor prognosis, such as breast cancer (Aaltonen et al., 2009; Agarwal et al., 2009; Suzuki et al., 2007), neuroblastoma (de et al., 2008) ), NSCLC (Cooper et al, 2009), cervical cancer (Zhao et al, 2006) and other cancers. It was found to be one of 11 genes included in a signature that predicts short-interval disease recurrence in patients with 12 different types of cancer. No specific information was found for gastric cancer.Cyclin D2(CCND2) Similar to other D-type cyclins (D1 and D3), CCND2 binds and activates cyclin-dependent kinase 4 (Cdk4) or Cdk6. This activity is required for G1/S transition. CCND2 has been found to be overexpressed in many tumors, including testicular and ovarian tumors (Sicinski et al., 1996), hematological malignancies (Hoglund et al., 1996; Gesk et al., 2006), and gastric cancer, which may be infected by H. pylori and is associated with poor prognosis (Yu et al., 2003). (Yu et al., 2001) (Oshimo et al., 2003) (Takano et al., 1999) (Takano et al., 2000).Cyclin E2(CCNE2) Similar to another E-type cyclin, CCNE1, CCNE2 binds and activates Cdk2. This activity peaks at the G1/S transition. Under healthy conditions, CCNE2 is undetectable in quiescent cells and can only be found in actively dividing tissues (Payton and Coats, 2002). It is often abnormally manifested in cancers such as breast cancer (Desmedt et al, 2006; Ghayad et al, 2009; Payton et al, 2002; Sieuwerts et al, 2006) and metastatic prostate cancer (Wu et al, 2009), and associated with poor prognosis.carcinoembryonic antigen-associated cell adhesion molecule 1 , 5 and 6 (CEACAM 1 , 5 and 6) CEACAM is a membrane-anchored glycoprotein that mediates cell-cell interactions and activates integrin signaling pathways (Chan and Stanners, 2007). It can also act as a receptor for pathogens such as E. coli (Berger et al., 2004) (Hauck et al., 2006) and can be involved in immune regulation (Shao et al., 2006). CEACAM5 and CEACAM6 have the function of promoting carcinogenesis. It inhibits anoikis (Ordonez et al., 2000), promotes metastasis (Marshall, 2003; Ordonez et al., 2000) and disrupts cell polarization and organization (Chan and Stanners, 2007). The role of CEACAM1 in cancer is unclear. It may be an early tumor suppressor and promote late metastasis formation, tumor immune escape and angiogenesis (Hokari et al., 2007; Liu et al., 2007; Moh and Shen, 2009). Its functional role depends on its isoform, as CEACAM1 occurs in 11 splice variants, and the ratio of these splice variants determines signaling outcomes (Gray-Owen and Blumberg, 2006; Leung et al., 2006; Neumaier et al, 1993; Nittka et al, 2008). The ratio of splice variants can vary in cancer (Gaur et al., 2008). CEACAM5 or CEACAM6 or both are overexpressed in up to 70% of all human tumors and are often associated with poor prognosis (Chan and Stanners, 2007; Chevinsky, 1991). Serum CEACAM5 is an established clinical marker for colon and rectal cancer, and its high levels indicate poor prognosis or recurrence (Chevinsky, 1991; Goldstein and Mitchell, 2005). It is also considered a marker for other entities, including gastric cancer, however, has limited ability to predict prognosis (Victorzon et al., 1995). CEACAM1 can be up- or down-regulated in cancer, depending on the cancer entity (Kinugasa et al., 1998) (Dango et al., 2008) (Simeone et al., 2007). (Han et al., 2008) found abundant CEACAM5 and CEACAM6 in 9 gastric cancer cell lines, but CEACAM1 was not detected. In contrast, analysis of primary tumor samples from 222 patients showed cytoplasmic or membrane staining for CEACAM1. The membrane-bound form is associated with enhanced angiogenesis (Zhou et al., 2009). A study by (Kinugasa et al., 1998) also showed that it is upregulated in gastric adenocarcinoma. In some tumors, CEACAM1 is downregulated in tumor cells, which results in upregulation of VEGF, and VEGF or hypoxic conditions can induce CEACAM1 expression in the adjacent endothelium. Thus, monoclonal antibodies directed against CEACAM1 can block VEGF-induced endothelial tube formation (Oliveira-Ferrer et al., 2004; Tilki et al., 2006; Ergun et al., 2000). In particular, CEACAM5 has been tested as a target for anticancer drugs, especially by vaccination methods. These studies showed that CEACAM5 may be a target of cellular immune responses (Cloosen et al., 2007; Marshall, 2003). An overview of the T cell epitopes of CEACAM5 is provided in (Sarobe et al., 2004).chloride channel 3(CLCN3) CLCN3 is a Cl channel that can be volume gated and contribute to regulated volume decrease (RVD) in response to cell volume increase under conditions such as the cell cycle or low osmolarity. However, this argument is controversial (Wang et al., 2004), and the volume-reducing channel activated during apoptosis differs from CLCN3 (Okada et al., 2006). The expression of CLCN3 changes during the cell cycle, which peaks in S phase (Wang et al., 2004). CLCN3 currents may be important in cancer-related processes in CLCN3-upregulated entities such as gliomas: tumor cells need to address proliferative volume increases, encounter hypotonic conditions, such as in peritumoral edema (Ernest et al., 2005; Olsen et al., 2003; Sontheimer, 2008). Furthermore, CLCN3 has been reported to enhance etoposide resistance by increasing acidification of the late endocytic compartment (Weylandt et al., 2007). siRNA-mediated blockade of CLCN3 expression reduces ex vivo metastasis of nasopharyngeal carcinoma cells (Mao et al., 2008).DNAJC10 DNAJC10 is a member of the supramolecular ER-associated degradation (ERAD) complex that recognizes and unfolds misfolded proteins for efficient retrotranslocation (Ushioda et al., 2008). This protein was shown to be elevated in hepatocellular carcinoma (Cunnea et al., 2007). Blockade of DNAJC10 expression in neuroectodermal tumor cells with siRNA increased the apoptotic response to the chemotherapeutic drug fenretinide (Corazzari et al., 2007). ERdj5 has been shown to reduce neuroblastoma cell survival by downregulating the unfolded protein response (UPR) (Thomas and Spyrou, 2009).eukaryotic translation initiation factor 2 subunit 3γ(EIF2S3) EIF2S3 is the largest subunit of the protein complex (EIF2) that recruits the initiating methionine-based tRNA to the 40S ribosomal subunit (Clemens, 1997). The effects of kinases (such as RNA-dependent protein kinase; PKR) that downregulate EIF activity can be pro-apoptotic and tumor-suppressive (Mounir et al., 2009). In gastric cancer, higher levels of phosphorylated and unphosphorylated EIF2 have been reported, and redistribution to the nucleus has been observed. This counter-regulation suggests that eIF2α is associated with gastrointestinal cancer (Lobo et al., 2000).eukaryotic translation initiation factor 3 subunit L(EIF3L) EIF3L is one of 10 to 13 subunits of EIF3, which is associated with the small ribosomal subunit. EIF3 plays a role in preventing premature association of large ribosomal subunits. EIF3L is one of five subunits that have been reported to be not required for EIF3 formation (Masutani et al., 2007). Screening results from an antisense library showed that down-regulation of EIF3L enhanced the antitumor activity of 5-fluorouracil in hepatocellular carcinoma cells (Doh, 2008).epidermal plaque protein (Epiplakin)1(EPPK1) EPPK1 is a gene of the plakin family of mostly unknown functions. Plaquein genes are known to function in interconnecting cytoskeletal filaments and anchoring them to the plasma membrane associative adhesive junctions (Yoshida et al., 2008).G protein-coupled receptors 39 (GPR39) GPR39 is a Gq protein-coupled receptor thought to be involved in gastrointestinal and metabolic functions (Yamamoto et al., 2009). Its signaling activates cAMP and serum response elements (Holst et al., 2004). The endogenous ligand for GPR39 may be zinc (Chen and Zhao, 2007). GPR39 is a novel suppressor of cell death that may represent a therapeutic target involved in processes including apoptosis and endoplasmic reticulum stress, such as cancer (Dittmer et al., 2008). GPR39 was found in human fetal kidney HFK and blastema-enriched stem-like wilms' tumor xenografted microarrays (Metsuyanim et al., 2009) and against various cell death stimuli It was up-regulated in the hippocampal cell line (Dittmer et al., 2008).ERBB2/HER2/NEU ERBB2 is a member of the EGFR family of receptor tyrosine kinases. Its ligand is not known, but it is a preferred heterodimeric partner for other members of the HER family (Olayioye, 2001). In malignant tumors, HER2 can act as an oncogene, primarily because high amplification of this gene induces protein overexpression in the cell membrane and subsequent acquisition of properties favorable to malignant cells (Slamon et al., 1989). Its overexpression is observed in a percentage of many cancers, including gastric cancer. In most cases, it is associated with poor prognosis (Song et al., 2010) (Yonemura et al., 1991) (Uchino et al., 1993) (Mizutani et al., 1993). ERBB2 is the target of the monoclonal antibody trastuzumab (marketed as Herceptin), which has been suggested in combination with chemotherapy as a treatment option for patients with HER2-positive advanced gastric cancer (Meza-Junco et al., 2009; Van Cutsem et al., 2009). Another monoclonal antibody, Pertuzumab, in late-stage clinical trials, inhibits dimerization of the HER2 and HER3 receptors (Kristjansdottir and Dizon, 2010). Selective overexpression of HER2 and HER3 in two histological types of gastric cancer (intestinal and diffuse) is highly correlated with poor prognosis (Zhang et al., 2009).beta-4 integrin (ITGB4) Integrins mediate cell adhesion and both outside-in and inside-out signal transduction. Integrin β-4 subunits heterodimerize with α-6 subunits. The resulting integrins promote hemidesmosome formation between the intracellular keratin cytoskeleton and basement membrane (Giancotti, 2007). Integrin beta-4 has dual functions in cancer, mediating stable adhesion on the one hand and pro-invasive signaling (including Ras/Erk and PI3K signaling) and angiogenesis on the other (Giancotti, 2007; Raymond et al., 2007). It is overexpressed in many tumors as well as in angiogenic endothelial cells and is often associated with progression and metastasis. β-4 integrin is highly expressed in gastric cancer, especially in stromal invasive cells (Giancotti, 2007; Tani et al., 1996). However, it is downregulated in undifferentiated types of gastric cancer with deepening tumor invasion, which may be attributed to the progressive epithelial-mesenchymal transition since β-4 integrin is an epithelial integrin (Yanchenko et al., 2009).lipocalin (LCN2) LCN2, or neutrophil gelatinase-associated lipocalin (NGAL), is an iron regulatory protein that exists in monomeric, homodimeric form, or as a heterodimer with MMP9 linked by disulfide bonds (Coles et al., 1999; Kjeldsen et al., 1993). Its expression is increased in several cancers and in some cases is associated with progression. Mechanistically, it stabilizes MMP9 and alters E-cadherin-mediated cell-cell adhesion, thereby increasing invasion. The complex of MMP-9 and LCN2 is associated with poorer survival in gastric cancer (Kubben et al., 2007) (Hu et al., 2009). Although a clear tumor-promoting role has been observed in various tumors in humans, several studies have demonstrated that LCN2 inhibits the pro-neoplastic factor HIF-1α, FA kinase phosphorylation, and VEGF synthesis, thus suggesting that under alternative conditions, LCN2 may play a role in, e.g. It also has abnormal anti-tumor and anti-metastatic effects in the neoplasia of colon, ovary and pancreas. (Bolignano et al., 2009; Tong et al., 2008). In addition to inhibiting tumor metastasis, LCN2 can also be used to inhibit tumor angiogenesis in ras-activated cancers (Venkatesha et al., 2006).Succinate dehydrogenase complex subunit C(SDHC) SDHC is one of the 4 nuclear-encoded subunits of succinate dehydrogenase (mitochondrial complex II), which transfers electrons from succinate to ubiquinone, thereby producing fumarate and ubiquinol. Succinate dehydrogenase deficiency can cause GIST (McWhinney et al., 2007). Familial gastrointestinal stromal tumors may be caused by mutations in the subunit genes SDHB, SDHC, and SDHD, and abdominal paragangliomas associated with gastrointestinal tumors may be caused by mutations in SDHC only (Pasini et al., 2008). In transgenic mice, mutant SDHC proteins generate oxidative stress and can promote nuclear DNA damage, mutagenesis and ultimately tumor formation (Ishii et al., 2005). Succinate dehydrogenase is considered a tumor suppressor (Baysal, 2003; Gottlieb and Tomlinson, 2005). Decreased levels of this enzyme complex can lead to tumor formation (Eng et al., 2003).PDZ binding kinase (PBK) PBKs are MEK3/6-related MAPKKs that activate p38 MAP kinases, such as those downstream of growth factor receptors (Abe et al., 2000; Ayllon and O'connor, 2007). JNK can be a secondary target (Oh et al., 2007). Since PBK is expressed in the testis in adults (see below), it is speculated to function in spermatogenesis (Abe et al., 2000; Zhao et al., 2001). Among other things, it promotes tumor cell proliferation and apoptosis resistance: it is phosphorylated and activated during mitosis, which is required for spindle formation and cytoplasmic division (Gaudet et al., 2000; Matsumoto et al., 2004; Park et al., 2009) (Abe et al., 2007). Other pro-growth and anti-apoptotic functions include downregulation of p53 and histone phosphorylation (Park et al., 2006; Zykova et al., 2006) (Nandi et al., 2007). PBK has been classified as a cancer-testis antigen (Abe et al., 2000; Park et al., 2006) and it has been found to be overrepresented in many cancers.polymerase (DNA guide )δ3 Auxiliary Subunit (POLD3) The DNA polymerase delta complex is involved in DNA replication and repair. It consists of proliferating cell nuclear antigen (PCNA), multi-unit replication factor C and 4-unit polymerase complexes (POLD1, POLD2, POLD3 and POLD4) (Liu and Warbrick, 2006). POLD3 plays a key role in the efficient recycling of PCNA during the pol δ dissociation-association cycle during prolonged DNA replication (Masuda et al., 2007).proteasome ( precursor, megalin factor )26S Subunit not ATP enzyme 14 (PSMD14) PSMD14 is a component of the 26S proteasome. It belongs to the 19S complex (19S cap; PA700) and is responsible for substrate deubiquitination during proteasomal degradation (Spataro et al., 1997). Overexpression of PSMD14 in mammalian cells affects cell proliferation and response to cytotoxic drugs such as vinblastine, cisplatin and doxorubicin (Spataro et al., 2002). Inhibition of PSMD14 by siRNA in HeLa cells resulted in decreased cell viability and increased levels of polyubiquitinated proteins (Gallery et al., 2007). Downregulation of PSMD14 by siRNA has a considerable effect on cell viability, leading to cell arrest in the G0-G1 phase and eventual aging (Byrne et al., 2010).proteasome ( precursor, megalin factor )26S Subunit not ATP enzyme 2 (PSMC2) PSMC2 is part of the 26S proteasome system. It is a member of the Triple A family of ATPases with chaperone-like activity. This unit has been shown to interact with several basal transcription factors and thus is involved in transcriptional regulation in addition to proteasome function. The 26S proteasome system in skeletal muscle has been shown to be activated by TNF-α (Tan et al., 2006). In HBx-transgenic mice harboring the hepatitis B regulatory gene HBx in the germline and developing HCC, PSMC2 and other proteasome subunits are up-regulated in tumor tissue (Cui et al., 2006). The mRNA content of the ATPase subunit PSMC2 of the 19S complex is increased in cancer cachexia (Combaret et al., 1999).protein tyrosine kinase 2 (PTK2) PTK2 is a non-receptor tyrosine kinase that regulates integrin signaling and promotes tumor growth, progression and metastasis ((Giaginis et al., 2009); (Hauck et al., 2002); (Zhao and Guan, 2009) ). PTK2 has been suggested as a marker of carcinogenesis and cancer progression (Su et al., 2002; Theocharis et al., 2009; Jan et al., 2009). Overexpression and/or increased activity occurs in a variety of human cancers, including gastric cancer. PTK2 also transduces signaling downstream of the gastrin receptor, which contributes to gastric cancer cell proliferation (Li et al., 2008b). 8% of gastric cancers showed Epstein-Barr virus (EBV). A subset of human gastric cancer cell lines infected with EBV exhibited increased phosphorylation of PTK2 (Kassis et al., 2002). The extent of PTK2 tyrosine phosphorylation in gastric epithelial cells was reduced by cagA positive H. pylori products.Tetraspanins 1(TSPAN1) and tetraspanins 8(TSPAN8) TSPAN1 and TSPAN8 belong to a family of tetraspanins, which are characterized by four transmembrane domains and intracellular N- and C-termini, and which play roles in multiple processes including cell adhesion, motility, activation, and tumor invasion. effect. It usually forms macromolecular complexes with other proteins, such as integrins, on the cell surface (Tarrant et al., 2003; Serru et al., 2000). The function of TSPAN1 is not known and may include a role in secretion (Scholz et al., 2009). TSPAN1 is overexpressed in several cancers and is often associated with stage, progression and worse clinical outcome. Notably, it was reported to be overrepresented in 56.98% of 86 gastric cancers, and overrepresentation was positively correlated with clinical stage, invasion, and lymph node status, but negatively correlated with survival and tumor differentiation grade (Chen et al., 2008) . It has also been reported that TSPAN8 is a metastasis-related gene in many types of tumors (PMID: 16467180). In gastrointestinal cancer, TSPAN8 expression is associated with poor prognosis (PMID: 16849554).zinc finger protein 598 (ZNF598) ZNF598 is a zinc finger protein of unknown function.disintegrin-like metalloprotease 10 (ADAM10) ADAM10 plays a role in angiogenesis, development and tumor formation. It is overexpressed in gastric cancer. A selective ADAM inhibitor against ADAM-10 is in clinical trials for cancer treatment (PMID: 19408347).matrix metalloproteinase 12 (MMP12) MMP12 is a zinc endopeptidase that degrades elastin and many other matrix and non-matrix proteins, and is involved in macrophage migration and angiogenesis inhibition (Chakraborti et al., 2003; Chandler et al., 1996; Sang, 1998). It also plays a role in pathological processes of tissue destruction such as asthma, emphysema and chronic obstructive pulmonary disease (COPD), rheumatoid arthritis and tumor growth (Cataldo et al., 2003; Wallace et al., 2008). MMP12 inhibitors are discussed as useful agents for the treatment of these conditions (Churg et al., 2007; Norman, 2009). MMP12 is often overexpressed in cancer, and its function in cancer is unclear. While it may be involved in matrix lysis, and thus metastasis, it can also inhibit tumor growth through the production of angiostatin, which negatively affects angiogenesis. Increased MMP12 expression in GC has been reported and shown to be favorable: it is inversely correlated with microvessel density, VEGF, tumor differentiation grade, vascular invasion, lymph node metastasis and recurrence. Patients overexpressing MMP12 demonstrated significantly better survival (Cheng et al, 2010; Zhang et al, 2007b; Zhang et al, 2007a).ribonucleotide reductase M2(RRM2) RRM2 is one of two subunits of ribonucleotide reductase that produces deoxyribonucleotides from ribonucleotides. RRM2 overexpression has been observed in tumors including gastric cancer, and this overexpression enhances metastatic potential (PMID: 18941749) (PMID: 19250552). Expressive blockade of RRM2 by siRNA slows tumor growth in various species (mouse, rat, monkey) (PMID: 17929316; PMID: 17404105).transmembrane protease serine 4 (TMPRSS4) TMPRSS4 is a type II transmembrane serine protease found on the cell surface that is highly expressed in several cancer tissues, including pancreatic, colon, and gastric cancers. The biological function of TMPRSS4 in cancer is not known. TMPRSS4 has 4 splice variants (Scott et al., 2001; Sawasaki et al., 2004). Performance in ovarian cancer correlates with stage (Sawasaki et al., 2004). TMPRSS4 is greatly elevated in lung cancer tissues, and siRNA expression of TMPRSS4 by siRNA treatment in lung and colon cancer cell lines is associated with reduced cell invasion and cell-matrix adhesion and regulation of cell proliferation (Jung et al., 2008). ).deiodinase iodothyronine II type (DIO2) DIO2 converts the hormone prothyroxine (T4) into the biologically active 3,3',5-triiodothyronine (T3). It is highly expressed in the thyroid and its expression and/or activity has been found to be counter-regulated in thyroid cancer (de Souza Meyer et al., 2005) (Arnaldi et al., 2005). However, it is also found in other tissues, such as normal lung and lung cancer (Wawrzynska et al., 2003) and brain tumors (Murakami et al., 2000).insulin-like growth factor 2mRNA binding protein 3(IGF2BP3) IGF2BP3 is mainly present in the nucleus, where it binds IGF2 mRNA and hinders its translation. It plays a role in embryogenesis and is downregulated in adult tissues. It can be up-regulated in tumor cells and is thus considered an oncofetal protein (Liao et al., 2005). It is found to be overrepresented in many cancers including gastric cancer, which is associated with poor prognosis (Jeng et al., 2009) (Jiang et al., 2006). IGF2BP3 derived peptides were tested in cancer vaccination studies (Kono et al., 2009).lamin B1(LMNB1) Lamin B1 is a lamin matrix protein and is involved in nuclear stability, chromatin structure and gene expression. In the early stages of apoptosis, lamin is degraded (Neamati et al., 1995) (Sato et al., 2008b; Sato et al., 2008a; Sato et al., 2009). LMNB1 is expressed to some extent in essentially all normal somatic cells, and preliminary studies suggest that it may be reduced in the pathogenesis of some cancers, including gastric cancer. In other cancers, such as hepatocellular carcinoma, LMNB1 was found to be upregulated and positively correlated with tumor stage, size and number of nodes (Lim et al., 2002).wingless MMTV integration site family members 5A WNT5A is a secreted signaling protein involved in developmental processes and tumor formation. Canonical WNT5A signaling via Frizzled and LRP5/LRP6 receptors maintains stem/progenitor cells, while atypical WNT5A signaling via Frizzled and ROR2/PTK/RYK receptors controls e.g. tissue polarity, cell polarity at the tumor-stroma interface Adhesion or migration, thereby leading to invasion (Katoh and Katoh, 2007). It can be a tumor suppressor in some cancers, but it is upregulated in others including gastric cancer, where it promotes progression and metastasis and leads to poor prognosis (Li et al., 2010) (Yamamoto et al., 2009) (Kurayoshi) et al., 2006).fibroblast activation protein α(FAP) FAP is an integral membrane gelatinase. Its putative serine protease activity may play a role in the control of fibroblast growth or epithelial-mesenchymal interactions during development, tissue repair and epithelial carcinogenesis (Scanlan et al., 1994). FAP has a potential role in cancer growth, metastasis and angiogenesis via cell adhesion and metastatic processes and rapid degradation of ECM components. It is present on tumor cells invading the ECM, in reactive cancer-associated fibroblasts, and in endothelial cells involved in angiogenesis, but not in inactive cells of the same type. (Dolznig et al., 2005; Kennedy et al., 2009; Rettig et al., 1993; Rettig et al., 1994; Scanlan et al., 1994; Zhang et al., 2010). FAP expression has been found in gastric cancer cells and related stromal fibroblasts (Zhi et al., 2010) (Chen et al., 2006) (Mori et al., 2004; Okada et al., 2003). In a mouse model, FAP-expressing cells were shown to be non-redundant immunosuppressive components of the tumor microenvironment (Kraman et al., 2010). In one mouse model of tumor vaccination, FAP was successfully used to target CD8+ and CD4+ T cell responses (Loeffler et al., 2006; Wen et al., 2010) (Lee et al., 2005) (Fassnacht et al., 2005).exosome protein complex subunit γ(COPG) ; exosome protein complex subunit γ2 (COPG2) ; exosome protein complex subunit β1 (COPB1) COPG, COPG2 and COPB1 are subunits of the exosome complex (also known as exosome complex 1; COPI) that binds to non-clathrin envelope vesicles. COPI enveloped vesicles mediate retrograde transport from the Golgi back to the ER and transport within the Golgi (Watson et al., 2004). It may also be involved in anterograde transport (Nickel et al., 1998). Retrograde trafficking in particular regulates EGF-dependent nuclear transport of EGFR, which binds to COPG (Wang et al., 2010). COPG was found to be overexpressed in lung cancer cells and lung cancer-associated microvascular endothelial cells (Park et al., 2008). The commonly expressed sequence of COPG2 is 80% identical to GOPG (Blagitko et al., 1999). COPG2 can replace possibly functionally redundant GOPG to form a COP I-like complex (Futatsumori et al., 2000). Blockade of COPB1 expression in cystic fibrosis transmembrane conductance regulator (CFTR) expressing cell lines presumes that exosome complexes are involved in CRTR trafficking to the plasma membrane (Denning et al., 1992) (Bannykh et al., 2000 ).ubiquitin-conjugating enzyme E2S (UBE2S) UBE2S is a cofactor for the anaphase-promoting complex (APC), an E3 ubiquitin ligase that regulates mitotic end and G1 by targeting cell cycle regulators. UBE2S lengthens ubiquitin chains after substrates are preubiquitinated by other components (Wu et al., 2010). UBE2S also targets VHL proteins to degrade the proteasome, thereby stabilizing HIF-1α (Lim et al., 2008) and may support proliferation, epithelial-mesenchymal transition and metastasis (Chen et al., 2009) (Jung et al., 2006) . UBE2S is overexpressed in several cancer entities.Kinesin family member 11(KIF11) KIF11 is required for assembly of the bipolar mitotic spindle. It has been found to be upregulated in several cancers, often in association with clinicopathological parameters (Liu et al., 2010) (Peyre et al., 2010). Small molecule inhibitors of KIF11, such as S-trityl-L-cysteine (STLC), developed as potential anticancer drugs, arrest cells in mitosis and promote cancer cell apoptosis (Tsui et al., 2009 ) (Wiltshire et al., 2010) (Ding et al., 2010). Clinically, KIF11 inhibitors show only modest activity (Kaan et al., 2010; Tunquist et al., 2010; Wiltshire et al., 2010; Zhang and Xu, 2008).disintegrin-like metalloprotease domain 8 (ADAM8) ADAM8 was originally thought to be an immune-specific ADAM, but it was later found to be present in other cell types as well, often in conditions involving inflammation and ECM remodeling, including cancer and respiratory diseases such as asthma (Koller et al., 2009) . A number of ADAM substances, including ADAM8, are expressed in human malignancies where they are involved in the regulation of growth factor activity and integrin function, thereby promoting cell growth and invasion, although the precise mechanisms of these phenomena are currently unclear (Mochizuki and Okada 2007). ADAM8 and other ADAMs are increased in mouse gastric tumors, possibly due to enhanced EGFR signaling (Oshima et al., 2011).cell division cycle 6 homologue ( Saccharomyces cerevisiae ) (CDC6) CDC6 is required for initiation of DNA replication. It is located in the nucleus during G1 but translocates into the cytoplasm at the onset of S phase. CDC6 also regulates replication checkpoint activation via interaction with ATR (Yoshida et al., 2010). CDC6 counterregulation results in inactivation of the INK4/ARF locus encoding 3 important tumor suppressor genes (p16INK4a and p15INK4b, both activators of the retinoblastoma pathway; and ARF, which is an activator of p53) (Gonzalez et al. , 2006). Expression blockade of CDC6 by siRNA prevents proliferation and promotes apoptosis (Lau et al., 2006). CDC6 is upregulated in cancers including gastric cancer (Nakamura et al., 2007) (Tsukamoto et al., 2008).F2R clotting factor II( Thrombin ) receptor (F2R) F2R, also known as protease-activated receptor (PAR1), is a G protein-coupled receptor. Signaling of PAR1, PAR2 and PAR4 can regulate calcium release or mitogen-activated protein kinase activation and contribute to platelet aggregation, vasodilation, cell proliferation, cytokine release and inflammation (Oikonomopoulou et al., 2010). F2R is thought to be involved in endothelial and tumor cell proliferation, as well as angiogenesis, and is overexpressed in many types of aggressive and metastatic tumors. The amount of its expression correlates directly with the aggressiveness of the cancer (Garcia-Lopez et al., 2010) (Lurje et al., 2010). In gastric cancer cells, F2R activation can trigger a cascade of responses that promote tumor cell growth and invasion, such as overexpression of NF-κB, EGFR, and tenascin C (TN-C) (Fujimoto et al., 2010). Thus, F2R expression in gastric cancer was found to correlate with wall invasion thickness, peritoneal spread and poor prognosis (Fujimoto et al., 2008). A mouse monoclonal anti-human PAR1 antibody (ATAP-2) that recognizes an epitope within the N-terminus of the thrombin receptor (SFLLRNPN) and the PAR1 agonist peptide TFLLRNPNDK have been described (Hollenberg and Compton 2002; Mari et al., 1996; Xu et al., 1995).olfactory protein 4(OLFM4) OLFM4, whose function is largely unknown, is overexpressed in inflamed colonic epithelial cells and in many human tumor types, especially those of the digestive system (Koshida et al., 2007). OLFM4 is a robust marker of stem cells in the human intestine and marks a subset of colorectal cancer cells (van der Flier et al., 2009). OLFM4 inhibits the pro-apoptotic protein GRIM-19 (Zhang et al., 2004) (Huang et al., 2010), regulates the cell cycle and promotes S-phase transition in cancer cell proliferation. Furthermore, OLFM4 is associated with cancer adhesion and metastasis (Yu et al., 2011b). Enhanced overexpression of OLFM4 in murine prostate tumor cells results in faster tumor formation in syngeneic hosts (Zhang et al., 2004). OLFM4 was found to be overexpressed in GC (Aung et al., 2006). Inhibition of OLFM4 expression can induce apoptosis in gastric cancer cells in the presence of cytotoxic agents (Kim et al., 2010). Furthermore, serum OLFM4 concentrations were increased in GC patients before surgery compared to healthy donors (Oue et al., 2009). OLFM4 was identified as a novel target gene for retinoic acid (RA) and the demethylating agent 5-aza-2'-deoxynucleus. These two agents have proven effective in the treatment of certain myeloid leukemia patients (Liu et al., 2010).Thy-1 cell surface antigen (THY1) Thy-1 (CD90) is a GPI-anchored glycoprotein found on many cell types including T cells, neurons, endothelial cells and fibroblasts. Thy-1 is involved in processes including adhesion, nerve regeneration, tumor growth, tumor suppression, migration, cell death and T cell activation. (Rege and Hagood 2006b; Rege and Hagood 2006a) (Jurisic et al., 2010). Thy-1 appears to be a marker of adult angiogenesis, but not embryonic angiogenesis (Lee et al., 1998). Furthermore, they are considered as various stem cells (mesenchymal stem cells, liver stem cells ("oval cells") (Masson et al., 2006), keratinocyte stem cells (Nakamura et al., 2006) and hematopoietic stem cells (Yamazaki et al., 2009) ) markers. Thy-1 is upregulated in several cancers, including gastric cancer and GIST, thus suggesting that Thy-1 may serve as a marker for these cancers (Yang and Chung 2008; Zhang et al., 2010) (Oikonomou et al., 2007).centrosome protein 250 kDa (CEP250) Cep250 plays a role in microtubule organizing center cohesion (Mayor et al., 2000). It is also known as centrosome Nek2-associated protein or C-Nap1 because it co-localizes with and is a substrate for the serine/threonine kinase Nek2. The connection between Nek2 kinase and its cytoplasmic regulated centrosome (Bahmanyar et al., 2008). At the onset of mitosis, C-Nap1 is phosphorylated and subsequently dissociated from the centrosome when the centrosome separates to form the bipolar spindle. In vitro experiments have shown that overexpression of Cep250 damages the microtubule organization at the centrosome (Mayor et al., 2002).hypoxia inducible factor 1α subunit ( basic helix - ring - helical transcription factor ) (HIF1A) HIF1A is the oxygen-sensitive subunit of hypoxia-inducible factor (HIF), a transcription factor that is active under hypoxic conditions commonly found in tumors. It mediates the transcription of more than 60 genes (eg, VEGF) related to survival, glucose metabolism, invasion, metastasis and angiogenesis. HIF1 is overexpressed in many cancers, is often associated with poor prognosis, and is considered a target of interest for pharmacological treatment (Griffiths et al., 2005; Quintero et al., 2004; Stoeltzing et al., 2004) (Zhong et al., 2004). 1999). In gastric cancer, HIF1A promotes angiogenesis (Nam et al., 2011) and is associated with tumor size, poor differentiation, tumor stage, shorter survival (Qiu et al., 2011) and metastasis (Wang et al., 2010) (Han et al. et al., 2006; Kim et al., 2009; Oh et al., 2008; Ru et al., 2007). It is also believed to lead to resistance to chemotherapeutic drugs such as 5-FU and reduce intracellular drug accumulation by inhibiting drug-induced apoptosis (Nakamura et al., 2009) (Liu et al., 2008). The HIF-1α-inhibitor 2-methoxy-estradiol significantly reduced the metastatic properties of gastric cancer cells (Rohwer et al., 2009).v-Ki-ras2 Kristin rat sarcoma virus oncogene homolog (KRAS) KRAS is a member of the small GTPases superfamily and is a proto-oncogene involved in the early steps of many signal transduction pathways that may be oncogenic, such as MAPK and AKT-mediated pathways. Single amino acid substitutions activate mutations resulting in transforming proteins that play a key role in various malignancies including gastric cancer (Capella et al., 1991). Oncogenic mutations in KRAS are uncommon in gastric cancer. In a subset of gastric cancers, the KRAS locus is amplified, resulting in overexpression of KRAS protein. Therefore, gene amplification may be the molecular basis for KRAS hyperactivation in gastric cancer (Mita et al., 2009). Mutated KRAS counterparts promote hypoxia-driven induction of VEGF (Kikuchi et al., 2009; Zeng et al., 2010). Mutated KRAS can also be detected in the serum or plasma of cancer patients, thus suggesting it as a readily available tumor marker (Sorenson, 2000). Peptide KRAS-001 was derived from only one of the two splice variants - NP_004976 (188 amino acids), but not from the splice variant NP_203524 (189 amino acids). These splice variants differ by their last exon, which is the location of KRAS001.No SMC condensin I complex subunit G(NCAPG) NCAPG is part of the Condensin I complex, which consists of chromosome structure maintenance (SMC) proteins and non-SMC proteins and regulates chromosome condensation and segregation during mitosis (Seipold et al., 2009). Overexpression of NCAPG has been found in many tumors, including nasopharyngeal carcinoma (Li et al., 2010), hepatocellular carcinoma (Satow et al., 2010) and melanoma (Ryu et al., 2007). In normal tissue, NCAPG showed the highest expression in the testis. It has been suggested as a possible proliferation marker and potential prognostic indicator in cancer (Jager et al., 2000).topoisomerase (DNA)IIα(TOP2A) and topoisomerase (DNA)Iiβ (TOP2B) TOP2A and TOP2B encode highly homologous isoforms of DNA topoisomerases, which control and change the topological state of DNA during transcription, and are involved in chromosome condensation, chromosomal separation, replication and transcription. Topoisomerases are the target of several anticancer drugs, such as anthracyclins, and various mutations have been associated with drug resistance (Kellner et al., 2002) (Jarvinen and Liu, 2006). TOP2A (but not TOP2B) is required for cell proliferation. It is located adjacent to the HER2 oncogene and is amplified in most HER2 amplified breast tumors as well as in breast tumors without HER2 amplification (Jarvinen and Liu, 2003) and many other tumor entities. Amplification and overexpression of TOP2A, which often occurs together with HER2, is also found in a subset of gastric cancers (Varis et al., 2002) (Liang et al., 2008).laminin γ2 (LAMC2) Laminin is the major non-collagenous component of the basement membrane. It is involved in cell adhesion, differentiation, migration, signaling and metastasis. The γ2 chain together with the α3 and β3 chains constitute laminin 5. LAMC2 promotes invasive growth of human cancer cells in vivo. It is highly expressed before invasion of human cancers, and its performance is associated with poor prognosis (Tsubota et al., 2010). Laminin 5 cleavage products produced by MMP-2 can activate EGFR signaling and promote cell motility (Schenk et al., 2003). In gastric cancer, LAMC2 can be induced by EGFR family members or Wnt5a, and its aggressive activity is dependent on LAMC2 (Tsubota et al., 2010) (Yamamoto et al., 2009).Aryl hydrocarbon receptor (AHR) AHR binds planar aromatic hydrocarbons, such as TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxene), and mediates genes including xenobiotic metabolic enzymes such as cytochrome P450 enzymes Transcribe. It also plays a role in cell cycle progression (Barhoover et al., 2010). AhR is thought to be partly related to the tumor-promoting activity of dioxane, as it has pro-proliferative and anti-apoptotic functions, and can lead to counter-regulation of cell-cell contacts, dedifferentiation, and enhanced motility (Watabe et al., 2010 ) (Dietrich and Kaina 2010) (Marlowe et al., 2008). AHR expression can be downregulated by TGF-beta (Dohr and Abel 1997; Wolff et al., 2001) and induced by Wnt or beta-catenin signaling (Chesire et al., 2004). AHR overexpression is found in many cancers, including gastric cancer, in which AHR is associated with frequent CYP1A1 expression (Ma et al., 2006). The expression and nuclear translocation of AHR is higher in gastric cancer than in normal tissues, and its expression gradually increases during carcinogenesis (Peng et al., 2009a). AhR pathway activation may enhance gastric cancer cell invasiveness via c-Jun-dependent induction of MMP-9 (Peng et al., 2009b). In mouse models, expression of constitutively active mutants of the aryl hydrocarbon receptor (CA-AhR) leads to gastric tumorigenesis, which is associated with increased mortality (Andersson et al., 2002; Kuznetsov et al., 2005). The function of AhR in cancer appears to be unclear, as some studies have also indicated that it has tumor suppressor activity (Gluschnaider et al., 2010) (Fan et al., 2010).Hyaluronic acid-mediated motor receptors (RHAMM) (HMMR) HMMR can be present on the cell surface where it binds hyaluronic acid (HA) and interacts with the HA receptor CD44. This interaction plays a role in processes such as cell motility, wound healing and invasion (Gares and Pilarski, 2000). In cells, HMMR is associated with the cytoskeleton, microtubules, centrosomes, and the mitotic spindle, and plays a role in controlling the integrity of the mitotic spindle. HMMR is overexpressed in several cancer tissues (Sohr and Engeland, 2008). HA is hypothesized to protect cancer cells from immune attack. Serum HA is often increased in metastatic patients (Delpech et al., 1997). HMMR has been identified as a promising tumor-associated antigen and possible prognostic factor in AML and CLL. Peptides derived from HMMR have been used in anti-leukemia vaccines. The in vitro immunogenicity of HMMR-001 was also tested, but not for vaccination (Tzankov et al, 2011) (Greiner et al, 2010; Schmitt et al, 2008; Tabarkiewicz and Giannopoulos, 2010) (Greiner et al, 2010) 2005). Excessive manifestations of HMMR are also found in several other cancers, which are often associated with poor prognosis. HMMR is also overexpressed in gastric cancer, often together with CD44, and is presumed to promote invasion and metastasis (Li et al., 1999) (Li et al., 2000a) (Li et al., 2000b).TPX2 microtubule-associated homologue ( clawed toad )(TPX2) TPRX2 is a proliferation-related protein expressed in the S, G(2) and M phases of the cell cycle and considered a proliferation marker (Cordes et al., 2010). TPRX2 is required for normal microtubule nucleation, such as for assembly of the mitotic spindle. TPX2 recruits and activates Aurora kinase A (Bird and Hyman, 2008; Moss et al., 2009). Phosphorylation of TPX2 with Polo-like kinase 1 increases its ability to activate aurora kinase A (Eckerdt et al., 2009). TPX2 is overexpressed in many tumor types and is often co-overexpressed with Aurora kinase-A (Asteriti et al., 2010). Examples of TPX2 overexpression that have been found (often associated with poor prognosis or later stages) are meningiomas (Stuart et al., 2010), lung cancer (Kadara et al., 2009) (Lin et al., 2006; Ma et al., 2006) (Manda et al., 1999) and hepatocellular carcinoma (Shigeishi et al., 2009b) (Satow et al., 2010) (Wang et al., 2003). Accordingly, the present invention relates to a peptide comprising a sequence selected from the group of SEQ ID NO: 1 to SEQ ID NO: 95, or having at least 80% homology with SEQ ID NO: 1 to SEQ ID NO: 95 , or a variant thereof that induces T cells to cross-react with the peptide, wherein the peptide is not a full-length polypeptide. The present invention further relates to a peptide comprising a sequence selected from the group of SEQ ID NO: 1 to SEQ ID NO: 95, or a variation thereof having at least 80% homology with SEQ ID NO: 1 to SEQ ID NO: 95 A variant, wherein the peptide or variant has a total length of 8 to 100, preferably 8 to 30, and optimally 8 to 14 amino acids. The present invention further relates to the previously described peptides capable of binding to molecules of the human major histocompatibility complex (MHC) of class I or II. The present invention further relates to the previously described peptide, wherein the peptide consists or consists essentially of the amino acid sequence of SEQ ID No. 1 to SEQ ID No. 95. The present invention further relates to the previously described peptide, wherein the peptide is modified and/or comprises non-peptide bonds. The present invention further relates to the previously described peptide, wherein the peptide is a fusion protein, in particular containing the N-terminal amino acid of the HLA-DR antigen-associated invariant chain (Ii ). The present invention further relates to a nucleic acid which encodes a peptide as previously described, provided that the peptide is not a fully human protein. The invention further relates to a nucleic acid as previously described, being DNA, cDNA, PNA, CAN, RNA, and possibly combinations thereof. The present invention further relates to an expression vector capable of expressing the previously described nucleic acid. The present invention further relates to a previously described peptide, a previously described nucleic acid or a previously described expression vector for use in medicine. The present invention further relates to a host cell comprising the aforementioned nucleic acid or the aforementioned expression vector. The present invention further relates to said host cell which is an antigen presenting cell. The present invention further relates to said host cell, wherein the antigen presenting cell is a dendritic cell. The invention further relates to a method of formulating one of said peptides, the method comprising culturing said host cell and isolating the peptide from the host cell or its culture medium. The present invention further relates to a method for the in vitro preparation of primed cytotoxic T lymphocytes (CTL), the method comprising in vitro linking the CTL to antigen-loaded human class I or II MHC molecules in suitable antigen-presenting cells The surface is expressed for a period of time sufficient to initiate CTL in an antigen-specific manner, wherein the antigen is any of the peptides. The present invention further relates to the method wherein the antigen is loaded into MHC class I or II molecules expressed on the surface of a suitable antigen presenting cell by binding to a sufficient amount of the antigen comprising the antigen presenting cell. The present invention further relates to the method, wherein the antigen presenting cell comprises an expression vector capable of expressing a peptide comprising SEQ ID NO 1 to SEQ ID NO 33 or said variant amino acid sequence. The present invention further relates to a priming cytotoxic T lymphocyte (CTL) prepared by said method, which lymphocyte selectively recognizes a cell that abnormally expresses a polypeptide containing one of said amino acid sequences. The present invention further relates to a method of killing target cells in a patient, wherein the target cells of the patient abnormally express a polypeptide comprising any of said amino acid sequences, the method comprising administering to the patient an effective amount of toxic T lymphocytes (CTLs) as described above. The invention further relates to the use of any of said peptides, said one nucleic acid, said one expression vector, said one cell, said one as a medicament or to manufacture a medicament to prime cytotoxic T lymphocytes. The invention further relates to such a method of use, wherein the medicament is a vaccine. The present invention further relates to such a method of use, wherein the agent has anticancer activity. The present invention further relates to such a use, wherein the cancer cells are gastric cancer cells, gastrointestinal cancer cells, colorectal cancer cells, pancreatic cancer cells, lung cancer cells or renal cancer cells. The present invention further relates to specific marker proteins that can be used as prognosis of gastric cancer. Furthermore, the present invention relates to these novel targets for use in cancer therapy. As provided herein, it has been described in the literature that compared to normal stomach and other living tissues (eg, liver, kidney, heart), the EIF2S3, LOC255308, EPHA2, ERBB2, ERBB3, F2R, FAP, HMMR, HSP90B1, IGF2BP3, ITGB4, KIF2C, KRAS, LAMC2, LCN2, MET, MMP11, MMP12, MMP3, MST1R, NUF2, OLFM4, PROM1, RRM2, THY1, The proteins encoded by TMPRSS4, TOP2A, TSPAN1, WNT5A, HIF1A and PTK2 are overexpressed in gastric cancer. By ABL1, ADAM10, ADAM8, AHR, ASPM, ATAD2, CCDC88A, CCNB1, CCND2, CCNE2, CDC6, CDK1, CEACAM1, CEACAM5, CEACAM6, CEACAM6, CLCN3, COL6A3, EPHA2, ERBB2, ERBB3, F2R, FAP, HIF1A, HMMR , HSP90B1, IGF2BP3, IQGAP3, ITGB4, KIF11, KIF2C, KRAS, LAMC2, LCN2, MET, MMP11, MMP3, MST1R, MUC6, NCAPG, NFYB, NUF2, OLFM4, PBK, PLK4, PPAP2C, PROM1, PTK2, RRM2, SIAH2 , THY1, TOP2A, TPX2, TSPAN1, TSPAN8, UBE2S, UCHL5 and WNT5A encoded proteins have been shown to have important roles in tumorigenesis because of their involvement in malignant transformation, cell growth, proliferation, angiogenesis or invasion of normal tissues. Likewise, there is evidence for cancer-related functions for proteins encoded by DNAJC10, EIF2S3, EIF3L, POLD3, PSMC2, PSMD14 and TMPRSS4. The proteins encoded by PROM1, WNT5A, SMC4, PPAP2C, GPR38, OLFM4 and THY1 were shown to be highly expressed and/or play an important role in stem cells and/or cancer stem cells. PROM1 is considered to be a marker of gastric cancer stem cells, but the data are still controversial. Cancer stem cells are a subset of tumor cells with the self-renewal potential required to maintain tumor growth. These cells reside in specialized and highly organized structures, the so-called cancer stem cell niches required to maintain the self-renewal potential of cancer stem cells. Proteins AHR, ASPM, ATAD2, CCNB1, CCND2, CCNE2, CDK1(CDC2), CEACAM1, CEACAM5, CEACAM6, CEACAM6, COL6A3, EPHA2, ERBB2, ERBB3, F2R, FAP, HIF1A, HMMR, HSP90B1, IGF2BP3, ITGB4, KIF11, The overexpression of KIF2C, KRAS, LAMC2, LCN2, LMNB1, MET, MMP11, MMP3, MST1R, MUC6, NCAPG, NUF2, OLFM4, PBK, PPAP2C, PROM1, PTK2, TMPRSS4, TPX2, TSPAN1, and WNT5A in tumors is associated with patient advanced disease stage and poor prognosis. Accordingly, the present invention proposes a method of identifying animals, preferably humans, who are likely to have gastric cancer. In one embodiment, the probability is determined to be 80% to 100%. One such method includes determining the level of at least one of the proteins MST1R, UCHL5, SMC4, NFYB, PPAP2C, AVL9, UQCRB, and MUC6 in a tumor sample from a subject animal. In one embodiment, the sample is obtained by radical surgery. In another embodiment, the sample is obtained by needle biopsy. A subject animal was identified as likely to have gastric cancer when the level measured for MST1R, UCHL5, SMC4, NFYB, PPAP2C, AVL9, UQCRB or MUC6 was upregulated by 20% or more relative to the level measured in benign epithelial cells of the same specimen. The more distinct proteins of the group consisting of MST1R, UCHL5, SMC4, NFYB, PPAP2C, AVL9, UQCRB, and MUC6 were up-regulated, the higher the probability that the test animals were identified as having gastric cancer. In one embodiment, MST1R, UCHL5, SMC4, NFYB, PPAP2C, AVL9, UQCRB or MUC6 levels are determined in situ. In another embodiment, MST1R, UCHL5, SMC4, NFYB, PPAP2C, AVL9, UQCRB or MUC6 levels are determined in vitro. In another embodiment, MST1R, UCHL5, SMC4, NFYB, PPAP2C, AVL9, UQCRB or MUC6 levels are determined in vivo. In a preferred embodiment, MST1R, UCHL5, SMC4, NFYB, PPAP2C, AVL9, UQCRB or MUC6 levels are determined using laser capture microscopy in conjunction with immunoblotting. In a preferred embodiment, MST1R, UCHL5, SMC4, NFYB, PPAP2C, AVL9, UQCRB or MUC6 levels are assayed using specific antibodies to MST1R, UCHL5, SMC4, NFYB, PPAP2C, AVL9, UQCRB or MUC6. In a preferred embodiment, MST1R, UCHL5, SMC4, NFYB, PPAP2C, AVL9, UQCRB or MUC6 levels are determined by PCR with primers encoding MST1R, UCHL5, SMC4, NFYB, PPAP2C, AVL9, UQCRB or MUC6 mRNA specific primers. In another preferred embodiment, the MST1R, UCHL5, SMC4, NFYB, PPAP2C, AVL9, UQCRB or MUC6 levels are determined with primer-containing nucleotide probes, wherein the probes encode MST1R, UCHL5, SMC4, NFYB, PPAP2C, Specific probes for AVL9, UQCRB or MUC6 mRNA. In one such embodiment, MST1R, UCHL5, SMC4, NFYB, PPAP2C, AVL9, UQCRB or MUC6 levels are determined using Northern blotting. In another embodiment, MST1R, UCHL5, SMC4, NFYB, PPAP2C, AVL9, UQCRB or MUC6 levels are determined using a ribonuclease protection method. In other embodiments, immunological tests such as enzyme-linked immunosorbent assay (ELISA), radioimmunoassay (RIA), and Western blotting may be used to detect samples of bodily fluids (eg, blood, serum, sputum, urine, or peritoneal fluid). ) MST1R, UCHL5, SMC4, NFYB, PPAP2C, AVL9, UQCRB and MUC6 polypeptides. Specimens, tissue samples, and cell samples (eg, ovaries, lymph nodes, ovarian surface epithelial cell debris, lung specimens, liver specimens, and any fluid samples containing cells (eg, peritoneal fluid, sputum, and pleural effusion) are acceptable Tested by disintegrating and/or lysing tissue or cell samples and detecting polypeptides using immunoassays (eg, ELISA, RIA or Western blotting). Such cell or tissue samples can also be analyzed using nucleic acid-based methods, eg, reverse transcription Polymerase chain reaction (RT-PCR) amplification, Northern hybridization, or slot or dot blot. To visualize the distribution of tumor cells in a tissue sample, diagnostic tests that preserve the tissue structure of the sample may be used (eg, immune tissue detection of gastric cancer marker polypeptides or mRNA using chemical staining, RNA in situ hybridization, or in situ RT-PCR techniques. For tumor localization in vivo, imaging studies, such as magnetic resonance imaging (MRI), may be used to introduce a Antibodies that specifically bind to MST1R, UCHL5, SMC4, NFYB, PPAP2C, AVL9, UQCRB or MUC6 polypeptides (especially those restricted to the cell surface), wherein the antibody is covalently bound or otherwise coupled to a paramagnetic tracer (or other suitable detectable moiety, depending on the imaging technique used); in addition, the location of unlabeled tumor marker-specific antibodies can be detected using a secondary antibody coupled to the detectable moiety. In addition, the present invention further proposes chimeric/fusion proteins/peptides comprising MST1R, UCHL5, SMC4, NFYB, PPAP2C, AVL9, UQCRB or MUC6 polypeptides, and fragments thereof (including functional, proteolytic and antigenic fragments). The fusion partner or fragment of the hybrid molecule provides stimulation of CD4⁺ Appropriate epitopes for T cells. CD4⁺ Stimulatory epitopes are well known in the art and include epitopes identified in tetanus toxoid. In a further preferred embodiment, the peptide is a fusion protein, especially comprising the N-terminal amino acid of the HLA-DR antigen-associated invariant chain (Ii). In one embodiment, the peptide of the invention is a truncated human protein or fusion protein of a protein fragment and another polypeptide portion (if the human polypeptide portion contains one or more of the inventive amino acid sequences). The present invention also includes antibodies to MST1R, UCHL5, SMC4, NFYB, PPAP2C, AVL9, UQCRB or MUC6 polypeptides, antibodies to chimeric/fusion proteins composed of MST1R, UCHL5, SMC4, NFYB, PPAP2C, AVL9, UQCRB or MUC6 polypeptides, and Antibodies to MST1R, UCHL5, SMC4, NFYB, PPAP2C, AVL9, UQCRB or MUC6 polypeptide fragments (including proteolytic and antigenic fragments) and antibodies to chimeric/fusion proteins/peptides comprising these fragments. In addition, methods of use of these antibodies against cancer, particularly gastric cancer prognosis, are also part of the present invention. Antibodies of the present invention may be polyclonal, monoclonal and/or chimeric. Immortal cell lines producing the monoclonal antibodies of the invention are also part of the invention. One of ordinary skill in the art will appreciate that in certain instances, higher expression of MST1R, UCHL5, SMC4, NFYB, PPAP2C, AVL9, UQCRB, or MUC6 as tumor marker genes is indicative of a poorer prognosis in subjects with gastric cancer. For example, higher levels of expression of MST1R, UCHL5, SMC4, NFYB, PPAP2C, AVL9, UQCRB, or MUC6 may indicate a relatively larger tumor size, a higher tumor burden (eg, more metastases), or a relatively more malignant tumor phenotype high. Higher overexpression of different proteins consisting of MST1R, UCHL5, SMC4, NFYB, PPAP2C, AVL9, UQCRB or MUC6 was associated with worse prognosis. The diagnostic and prognostic methods of the present invention involve the use of known methods, such as antibody-based methods, to detect MST1R, UCHL5, SMC4, NFYB, PPAP2C, AVL9, UQCRB and MUC6 polypeptides, as well as nucleic acid hybridization and/or amplification-based method to detect the mRNAs of MST1R, UCHL5, SMC4, NFYB, PPAP2C, AVL9, UQCRB and MUC6. In addition, since the rapid destruction of tumor cells often leads to the production of autoantibodies, the gastric cancer tumor markers of the present invention can be used for serological detection (eg, ELISA test of subject serum) to detect anti-MST1R, UCHL5, SMC4, Autoantibodies to NFYB, PPAP2C, AVL9, UQCRB or MUC6. Levels of MST1R, UCHL5, SMC4, NFYB, PPAP2C, AVL9, UQCRB and MUC6 polypeptide-specific antibodies are at least about 3-fold (preferably at least 5-fold or 7-fold, most preferably at least 10-fold or 20-fold) higher than in the control sample, This level suggests gastric cancer. Cell-surface localized, intracellular, and secreted MST1R, UCHL5, SMC4, NFYB, PPAP2C, AVL9, UQCRB, and MUC6 polypeptides are all potentially useful in biopsy analysis, e.g., tissue or cell samples (including fluid samples such as those obtained from peritoneal fluid). ) to identify tissue or cell specimens containing gastric cancer cells. Specimens may be analyzed as intact tissue or whole cell samples, which may also be disintegrated and/or lysed as required for a particular type of diagnostic test. For example, a specimen or sample may be analyzed for MST1R, UCHL5, SMC4, NFYB, PPAP2C, AVL9, UQCRB, and MUC6 polypeptide or mRNA levels in whole tissue or whole cells by in situ, immunohistochemistry, in situ hybridization for mRNA method or in situ RT-PCR. The skilled artisan knows how to process tissues or cells for analysis at the polypeptide or mRNA level, using immunological methods (such as ELISA, western blotting or equivalent), or using nucleic acid-based analysis methods (such as RT-PCR, Northern hybridization or trough or dot blot) to analyze mRNA levels. Kit to measure expression levels of MST1R, UCHL5, SMC4, NFYB, PPAP2C, AVL9, UQCRB and MUC6. The present invention proposes a kit for detecting elevated expression levels of MST1R, UCHL5, SMC4, NFYB, PPAP2C, AVL9, UQCRB and MUC6 as marker genes for gastric cancer in a subject. A kit for detecting a gastric cancer marker polypeptide preferably comprises an antibody that specifically binds to the selected gastric cancer marker polypeptide. A kit for detecting gastric cancer marker mRNA preferably comprises one or more nucleic acids (e.g., one or more oligonucleotide primers or probes) that specifically hybridize to MST1R, UCHL5, SMC4, NFYB, PPAP2C, AVL9, UQCRB, and MUC6 mRNA. needles, DNA probes, RNA probes, or RNA-producing probe templates). In particular, antibody-based kits can be used to detect whether or not to present, and/or measure MST1R, UCHL5, SMC4, NFYB, PPAP2C, AVL9, UQCRB, and MUC6 that specifically bind to antibodies or immunoreactive fragments thereof. The kit may contain an antibody reactive with the antigen and a reaction to detect the antibody containing the antigen. The kit may be an ELISA kit, which may contain controls (eg, specified amounts of a specific gastric cancer marker polypeptide), primary and secondary antibodies (where appropriate), any other necessary reagents as described above, such as: detectable motifs , enzyme substrates and colored reagents. Additionally, a diagnostic kit can be a kit consisting generally of the components and reagents described herein. Nucleic acid-based kits can be used to detect and/or measure MST1R by detecting and/or measuring mRNA for BMST1R, UCHL5, SMC4, NFYB, PPAP2C, AVL9, UQCRB, and MUC6 in samples such as tissue or cell specimens , UCHL5, SMC4, NFYB, PPAP2C, AVL9, UQCRB and MUC6 expression levels. For example, RT-PCR kits that detect elevated expression of MST1R, UCHL5, SMC4, NFYB, PPAP2C, AVL9, UQCRB, and MUC6 preferably contain sufficient oligonucleotide primers to reverse transcribe gastric cancer mRNA to cDNA as well as for gastric cancer marker cDNA. PCR amplification is also performed, preferably including control PCR template molecules and primers for appropriate negative and positive controls as well as internal controls for quantification. One of ordinary skill in the art would understand how to select appropriate primers for reverse transcription and PCR reactions, as well as appropriate control reactions. Such guidance can be found, for example, in F. Ausubel et al., Current Protocols in Molecular Biology, New York, N.Y., 1997. Many mutants of RT-PCR are well known in the art. Immunotoxins can be targeted to deliver MST1R, UCHL5, SMC4, NFYB, PPAP2C, AVL9, UQCRB and MUC6 as therapeutic targets for the prevention and treatment of gastric cancer. For example, an antibody molecule that specifically binds to cell surface localized MST1R, UCHL5, SMC4, NFYB, PPAP2C, AVL9, UQCRB, and MUC6 polypeptides can be covalently bound to radioisotopes or other toxic compounds. The antibody conjugate is administered to a subject such that binding of the antibody to its cognate gastric cancer polypeptide results in targeted delivery of a therapeutic compound to gastric cancer cells, thereby treating ovarian cancer. Therapeutic ingredients can be toxins, radioisotopes, drugs, chemicals, or proteins (see, eg, Bera et al. "Pharmacokinetics and antitumor activity of a bivalent disulfide-stabilized Fv immunotoxin with improved antigen binding to erbB2" Cancer Res. 59:4018 -4022 (1999). For example, the antibody can be linked or covalently bound to a bacterial toxin (eg, diphtheria toxin, Pseudomonas aeruginosa exotoxin A, cholera toxin) or a phytotoxin (eg, ricin) to bind The toxin is targeted for delivery to cells expressing MST1R, UCHL5, SMC4, NFYB, PPAP2C, AVL9, UQCRB and MUC6. This immunotoxin can be delivered to cells, and once bound to the cell surface localized gastric cancer marker polypeptide, the toxin conjugated to the gastric cancer marker-specific antibody will be delivered to the cell. In addition, for any MST1R, UCHL5, SMC4, NFYB, PPAP2C, AVL9, UQCRB, and MUC6 polypeptides that contain a specific ligand (e.g., ligands that bind to cell surface localized proteins), the ligand can be substituted for the antibody to Toxic compounds target gastric cancer cells as described above. The term "antibody" herein is broadly defined to include both polyclonal and monoclonal antibodies. In addition to intact immunoglobulin molecules, the term "antibody" includes such immunoglobulin molecules and fragments or polymers of humanized immunoglobulin molecules so long as they exhibit any of the desired properties described herein (eg, gastric cancer Specific binding of marker polypeptides, delivery of toxins to gastric cancer cells and/or activity of gastric cancer marker polypeptides when expression levels of gastric cancer marker genes are increased). Wherever possible, antibodies of the invention can be purchased from commercial sources. Antibodies of the present invention may also be prepared using known methods. The skilled artisan will appreciate that full length gastric cancer marker polypeptides or fragments thereof can be used to prepare the antibodies of the invention. The polypeptides used to generate the antibodies of the present invention can be purified in part or in whole from natural sources, or can be produced using recombinant DNA techniques. For example, cDNA encoding MST1R, UCHL5, SMC4, NFYB, PPAP2C, AVL9, UQCRB, and MUC6 polypeptides, or a fragment thereof, can be expressed in prokaryotic cells (eg, bacteria) or eukaryotic cells (eg, yeast, insect, or mammalian cells) ), after which the recombinant protein can be purified and used to generate a monoclonal or polyclonal antibody preparation that specifically binds to the gastric cancer marker polypeptide used to generate the antibody. Those skilled in the art will appreciate that two or more distinct sets of monoclonal or polyclonal antibodies maximize the specificity and affinity required for an intended use (eg, ELISA, immunohistochemical , in vivo imaging, immunotoxin therapy) the possibility of antibodies. Antibodies are tested for their desired activity by known methods (eg, ELISA, immunohistochemistry, immunotherapy, etc.; for further guidance on generating and testing antibodies, see, eg, Harlow and Lane, Antibodies : A Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1988). For example, the antibody can be detected by ELISA, immunoblotting, immunohistochemical staining of formalin-fixed gastric cancer samples, or frozen tissue sections. Following initial in vitro characterization, antibodies for therapeutic or in vivo diagnostic use are tested according to known clinical testing methods. As used herein, the term "monoclonal antibody" refers to an antibody obtained from a large number of homogeneous antibodies, ie, a population of antibodies composed of identical antibodies, except for natural mutations that may be presented in small amounts. Monoclonal antibodies as described herein specifically include "chimeric" antibodies in which a portion of the heavy and/or light chains are identical (homogeneous) to the corresponding sequences of antibodies obtained from a particular species or belonging to a particular antibody class and subclass, At the same time, the remaining chains are identical (homogeneous) to the corresponding sequences of antibodies obtained from other species or of antibodies belonging to specific antibody classes and subclasses, and fragments of these antibodies, as long as they exhibit the expected antagonistic activity (US Pat. No. 4,816,567). The monoclonal antibodies of the present invention may be prepared using the hybridoma method. In the hybridoma method, a mouse or other suitable host animal is typically immunized with an immunization agent to elicit the production or production of antibodies that will specifically bind to the immunization agent. Alternatively, lymphocytes can be immunized in vitro. Monoclonal antibodies can also be prepared by recombinant DNA methods, as described in US Pat. No. 4,816,567. DNA encoding the monoclonal antibodies of the invention can be readily isolated and sequenced using conventional procedures (eg, by using oligonucleotide probes that bind specifically to genes encoding murine antibody heavy and light chains). In vitro methods are also suitable for preparing monovalent antibodies. Digestion of antibodies to produce fragments of antibodies, particularly Fab fragments, can be accomplished using conventional techniques known in the art. For example, digestion can be accomplished by using papain. Examples of papain digestion are described in WO 94/29348, published December 22, 1994, and in US Pat. No. 4,342,566. Papain digestion of antibodies typically yields two identical antigen-binding fragments, termed Fab fragments (each with an antigen-binding site) and residual Fc fragments. Pepsin treatment produces a fragment that has two antigen-binding sites and still has the ability to cross-link the antigen. Antibody fragments, whether or not they are attached to other sequences, may include insertions, deletions, substitutions, or other selective modifications of specific regions or specific amino acid residues, provided that the activity of the fragment is comparable to that of the unmodified antibody or antibody fragment. than no significant change or damage. These modifications can provide some additional properties, such as: deletion/addition of amino acids that can bind disulfide bonds to increase their biological lifespan, alter their secretory properties, etc. In any case, the antibody fragment must possess biologically active properties, such as: binding activity, modulation of binding of the binding domain, etc. The functional or active region of an antibody can be determined by genetic mutation of specific regions of the protein, followed by expression and testing of the expressed polypeptide. These methods are well known to those skilled in the art and may involve site-specific genetic mutation of the nucleic acid encoding the antibody fragment. The antibodies of the present invention may further include humanized antibodies or human antibodies. Humanized forms of non-human (eg, murine) antibodies are chimeric antibody immunoglobulins, immunoglobulin chains or fragments thereof (eg, Fv, Fab, Fab' or other antigen-binding sequences of antibodies) containing Minimal sequence obtained in human immunoglobulin. Humanized antibodies include human immunoglobulins (acceptor antibodies) in which residues from the acceptor complementarity-determining regions (CDRs) are replaced by residues from a non-human species (donor antibodies) (eg, small proteins with specificity, affinity, and capacity for them). murine, rat or rabbit) residue substitutions in the CDRs. In certain instances, Fv framework (FR) residues of the human immunoglobulin are replaced by corresponding non-human residues. Humanized antibodies may also include residues found in neither the acceptor antibody nor the import CDR or framework sequences. In general, a humanized antibody will include substantially all of at least one, and usually two, variable domains, wherein all or nearly all of the CDR regions correspond to regions of the non-human immunoglobulin and all or nearly all of the FRs The regions are all regions of the same sequence of human immunoglobulins. Ideally, the humanized antibody will also include at least a portion of an immunoglobulin constant region (Fc), typically a portion of the constant region of a human immunoglobulin. Methods of humanizing non-human antibodies are well known in the industry. Generally, humanized antibodies have one or more amino acid residues introduced from a non-human source. These non-human amino acid residues are often referred to as "import" residues and are usually obtained from an "import" variable domain. Humanization can essentially be accomplished by substituting rodent CDRs or CDR sequences with the corresponding human antibody sequences. Thus, such "humanized" antibodies are chimeric antibodies (US Pat. No. 4,816,567) in which substantially less than the entire human variable domain has been replaced by corresponding sequences from a non-human species. In practice, humanized antibodies are usually human antibodies in which some CDR residues and possibly some FR residues are replaced by residues from analogous sites in rodent antibodies. Transgenic animals (eg, mice) that produce fully human antibodies after immunization in the absence of endogenous immunoglobulin production can be used. For example, it has been described that homozygous deletion of the antibody heavy chain linker region gene in chimeric and germline mutant mice results in complete inhibition of endogenous antibody production. Transfer of human germline immunoglobulin gene arrays in this strain variant mouse will result in the production of human antibodies following antigen challenge. Human antibodies can also be produced in phage display libraries. The antibodies of the present invention are preferably administered to a subject in the form of a pharmaceutically acceptable carrier. Typically, an appropriate amount of a pharmaceutically acceptable salt is used in the formulation to render the formulation isotonic. Examples of pharmaceutical carriers include physiological saline, Ringer's solution and dextrose solution. The pH of the solution is preferably about 5 to 8, more preferably about 7 to 7.5. In addition, carriers also include sustained release formulations such as solid hydrophobic polymer semipermeable matrices containing the antibody, wherein the matrices are in the form of tangible objects such as films, liposomes or microparticles. It is well known to those skilled in the art that certain carriers may be more preferred, depending, for example, on the route of administration and concentration of the antibody. The antibody can be administered to a subject, patient or cell by injection (eg, intravenous, intraperitoneal, subcutaneous, intramuscular) or by other methods such as infusion, ensuring that it is delivered to the bloodstream in an effective form. These antibodies can also be administered by intratumoral or peritumoral routes, thereby exerting local and systemic therapeutic effects. Topical or intravenous injection is preferred. Effective doses and schedules of antibody administration can be determined empirically, and making such determinations is within the skill of the art. Those skilled in the art will appreciate that the dose of antibody that must be administered will vary depending on factors such as the subject receiving the antibody, the route of administration, the antibody being used, and the particular type of other drug being used. Typical daily doses of antibodies used alone may range from about 1 µg/kg to up to 100 mg/kg of body weight or more, depending on the factors mentioned above. Following administration of an antibody to treat gastric cancer, the efficacy of the therapeutic antibody can be assessed by different methods well known to the skilled artisan. For example, the size, number and/or distribution of gastric cancer in a subject receiving treatment can be monitored using standard tumor imaging techniques. Antibodies administered as a result of therapy that prevent tumor growth, cause tumor shrinkage, and/or prevent the development of new tumors compared to the course of disease when the antibody is not administered is an effective antibody for the treatment of gastric cancer. Because proteins ABL1, ADAM10, AHR, CCND2, CDC6, CDK1, CEACAM1, CEACAM5, CEACAM6, CEACAM6, COL6A3, EIF2S3, LOC255308, EPHA2, ERBB2, ERBB3, F2R, FAP, HMMR, HSP90B1, IGF2BP3, ITGB4, KIF2C, KRAS, LAMC2, LCN2, MET, MMP11, MMP12, MMP3, MST1R, NUF2, OLFM4, PROM1, RRM2, THY1, TMPRSS4, TOP2A, TSPAN1, WNT5A, HIF1A and PTK2 were shown to be highly elevated in at least one subset of gastric cancer tissue compared to normal tissue expression, so inhibition of its expression or activity can be incorporated into any therapeutic strategy for the treatment or prevention of gastric cancer. The rationale for antisense therapy is based on the assumption that sequence-specific inhibition of gene expression (either by transcription or translation) may be achieved by hybridization between genomic DNA or mRNA and complementary antisense species. The formation of this hybrid nucleic acid duplex interferes with the transcription of the target tumor antigen-encoding genomic DNA, or the processing/transportation/translation and/or stability of the target tumor antigen mRNA. Antisense nucleic acids can be delivered in a variety of ways. For example, antisense oligonucleotides or antisense RNAs can be administered directly (eg, by intravenous injection) to a subject in a manner that is taken up by tumor cells. Alternatively, viral or plasmid vectors encoding antisense RNA (or RNA fragments) can be introduced into cells in vivo. Antisense effects can also be induced by sense sequences; however, the degree of phenotypic change varies widely. Phenotypic changes induced by effective antisense therapy can be assessed based on, for example, changes in target mRNA levels, target protein levels, and/or target protein activity levels. In a specific embodiment, antisense gene therapy can inhibit the function of gastric cancer markers by directly administering antisense gastric cancer marker RNA to the subject. Tumor marker antisense RNA can be made and isolated by any standard technique, but the easiest method of manufacture is in vitro transcription using tumor marker antisense cDNA under the control of a highly efficient promoter (eg, the T7 promoter). Administration of tumor marker antisense RNA to cells can be carried out by any of the methods of direct nucleic acid administration described below. Alternative strategies to inhibit MST1R, UCHL5, SMC4, NFYB, PPAP2C, AVL9, UQCRB or MUC6 using gene therapy approaches involve anti-MST1R, UCHL5, SMC4, NFYB, PPAP2C, AVL9, UQCRB or MUC6 antibodies or anti-MST1R, UCHL5, Intracellular expression of a portion of SMC4, NFYB, PPAP2C, AVL9, UQCRB or MUC6 antibodies. For example, a gene (or gene fragment) encoding a monoclonal antibody that specifically binds to a MST1R, UCHL5, SMC4, NFYB, PPAP2C, AVL9, UQCRB or MUC6 polypeptide and inhibits its biological activity, its specificity (e.g., tissue-specific or tumor-specific) specific) gene regulatory sequences are placed under transcriptional control within the nucleic acid expression vector. The vector is then administered to the subject for uptake by gastric cancer cells or other cells, which then secrete anti-MST1R, UCHL5, SMC4, NFYB, PPAP2C, AVL9, UQCRB or MUC6 antibodies and block MST1R, UCHL5, SMC4, NFYB , PPAP2C, AVL9, UQCRB and MUC6 polypeptide biological activity. Preferably, MST1R, UCHL5, SMC4, NFYB, PPAP2C, AVL9, UQCRB and MUC6 are present on the extracellular surface of gastric cancer cells. In the methods described above, wherein exogenous DNA is administered into and taken up by cells of a subject (ie, (ie, gene transduction or transfection), the nucleic acid of the invention may be in the form of naked DNA or the nucleic acid may be The nucleic acid is delivered to cells in a vector to inhibit the expression of gastric cancer marker proteins. The vector can be a commercially available formulation, such as an adenoviral vector (Quantum Biotechnology, Laval, Quebec, Canada). The nucleic acid or vector can be delivered through a variety of The mechanism is delivered into cells. For example, commercially available liposomes can be used, such as: LIPOFECTIN, LIPOFECTAMINE (GIBCO-25 BRL company, Gaithersburg, Md.), SUPERFECT (Qiagen company, Hilden, Germany) and TRANSFECTAM (Promega Biotec company, Madison, Wis.) and other liposomes developed according to standard procedures in the art, are delivered through these liposomes. In addition, nucleic acid or carrier of the present invention can be delivered by in vivo electroporation, and this technology can be obtained from Genetronics company (San Diego, Calif. ) and delivered by means of a SONOPORATION machine (ImaRx Pharmaceuticals, Tucson, Arizona). For example, vectors can be delivered by viral systems (such as retroviral vector systems that can encapsulate recombinant retroviral genomes). Recombinant retroviruses Can be used for infection, so as to be delivered to the infected cell antisense nucleic acid that suppresses the expression of MST1R, UCHL5, SMC4, NFYB, PPAP2C, AVL9, UQCRB or MUC6. Of course, the nucleic acid that is changed is accurately imported into mammalian cells and is not limited to Retroviral vectors are used. A wide range of other techniques are available for this procedure, including the use of adenoviral vectors, adeno-associated virus (AAV) vectors, lentiviral vectors, pseudotyped retroviral vectors. Physical transduction can also be used Techniques such as liposome delivery and receptor-mediated and other mechanisms of endocytosis. The present invention can be used in conjunction with any of these techniques or other commonly used gene transfer methods. The antibody can also be used in in vivo diagnostic assays. Generally speaking , the antibody is labeled with a radionuclide (eg:¹¹¹ In,⁹⁹ Tc,¹⁴ C.¹³¹ I.³ H.³² P or³⁵ S), thereby allowing tumor localization by immunoscintigraphy. In one embodiment, the antibody or fragment therein binds to the extracellular domains of two or more MST1R, UCHL5, SMC4, NFYB, PPAP2C, AVL9, UQCRB and MUC6 targets with an affinity value (Kd) of less than 1 x 10 µM. Diagnostic antibodies can be labeled with probes suitable for detection by various imaging methods. Probe detection methods include, but are not limited to, fluorescence, light, confocal and electron microscopy methods; magnetic resonance imaging and spectroscopy techniques; fluoroscopy, computed tomography, and positron emission tomography. Suitable probes include, but are not limited to, luciferin, rhodamine, eosin and other fluorophores, radioisotopes, gold, gadolinium and other rare earths, paramagnets, fluorine-18 and other positron emitting radionuclides. In addition, probes may be bifunctional or multifunctional and detectable using more than one of the above methods. These antibodies can be labeled directly or indirectly with the probes described. Attachment of antibody probes includes covalent attachment of probes, fusion of probes into antibodies, and covalent attachment of chelating compounds to bind probes, as well as other methods well known in the art. For immunohistochemical methods, disease tissue samples may be fresh or frozen or may be embedded in paraffin and fixed with a preservative such as formalin. Fixed or embedded sections include samples contacted with labeled primary and secondary antibodies for in situ detection of MST1R, UCHL5, SMC4, NFYB, PPAP2C, AVL9, UQCRB, and MUC6 protein expression. Accordingly, the present invention provides a peptide comprising a sequence selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 95, or 85%, preferably 90% thereof with SEQ ID NO: 1 to SEQ ID NO: 95 And more preferably a variant with 96% homology, or a variant thereof that induces T cells to cross-react with the peptide. The peptides of the present invention have the ability to bind to major histocompatibility complex (MHC) class I molecules. In the present invention, the term "homology" refers to the degree of identity between two amino acid sequences, such as peptide or polypeptide sequences. The aforementioned "homologous" is determined by aligning two sequences adjusted under ideal conditions with the sequences to be compared. Here, the sequences to be compared may have additions or deletions (eg, gaps, etc.) in the optimal alignment of the two sequences. Such sequence homology can be calculated by creating an alignment using the algorithm of ClustalW et al. It is also possible to use general sequence analysis software, more specifically Vector NTI, GENETYX or analysis tools provided by public repositories. One skilled in the art can assess whether T cells induced by a particular peptide variant can cross-react with the peptide itself (Fong et al. 8809-14); (Appay et al. 1805-14; Colombetti et al. 2730-38; Zaremba et al. 4570-77). The inventors refer to a "variant" of a given amino acid sequence in which the side chain of one or more amino acid residues, etc. is altered by substitution with the side chain or other side chains of another natural amino acid residue, such that the peptide It is still possible to bind to HLA molecules in much the same way as peptides containing the given amino acid sequences SEQ ID NOs: 1 to 33. For example, a peptide may be modified so as to at least maintain (if not enhance) its ability to interact and bind to the binding groove of a suitable MHC molecule such as HLA-A or -DR, and to at least maintain (if not enhance) its ability to interact with initiation TCR binding of CTLs. These CTLs can then cross-react with cells and killer cells that express polypeptides comprising the native amino acid sequences of homologous peptides as defined in the present invention. As described in the scientific literature (Rammensee, Bachmann, and Stevanovic) and databases (Rammensee et al. 213-19), certain sites of HLA-A-binding peptides are often anchor residues that form an HLA-binding A core sequence commensurate with the binding motif of the groove, which is defined by the polar, electrophysical, hydrophobic, and steric properties of the polypeptide chains that make up the binding groove. Thus, one skilled in the art can modify the amino acid sequences shown in SEQ ID Nos: 1 to 95 by maintaining known anchor residues, and can determine whether these variants retain the ability to bind to MHC-I or II molecules. Variants of the present invention retain the ability to bind to TCRs that initiate CTLs which can then cross-react with and kill cells expressing a polypeptide comprising the native amino acid sequence of a homologous peptide as defined herein. These amino acid residues that do not substantially interact with T cell receptors can be modified by substituting another amino acid that has little effect on T cell responses and does not prevent binding to the relevant MHC. Thus, subject to certain limitations, a peptide of the invention may be any peptide comprising a given amino acid sequence or portion or variant thereof (this term used by the inventors includes oligopeptides or polypeptides). Table 3: Peptide variants and motifs according to SEQ ID NOs: 1 to 33       Location 1 2 3 4 5 6 7 8 9 10 CDC2-001 Peptide code L Y Q I L Q G I V F SEQ ID 1 Variants       F                                                             L                                     I             F                      L             F                      I       Location 1 2 3 4 5 6 7 8 9    ASPM-002 Peptide code S Y N P L W L R I    SEQ ID 2 Variants       F                                                          L                                     F                F                   L                F                   F          Location 1 2 3 4 5 6 7 8 9    UCHL5-001 Peptide code N Y L P F I M E L    SEQ ID 3 Variants       F                                                          F                                     I                F                   F                F                   I          Location 1 2 3 4 5 6 7 8 9    MET-006 Peptide code S Y I D V L P E F    SEQ ID 4 Variants       F                                                          L                                     I                F                   F                F                   I          Location 1 2 3 4 5 6 7 8 9    PROM-001 Peptide code S Y I I D P L N L    SEQ ID 5 Variants       F                                                          F                                     I                F                   F                F                   I          Location 1 2 3 4 5 6 7 8 9 10 MMP11-001 Peptide code V W S D V T P L T F SEQ ID 6 Variants       Y                                     F                                                             L                                     I             Y                      L             Y                      I             F                      L             F                      I       Location 1 2 3 4 5 6 7 8 9    MST1R-001 Peptide code N Y L L Y V S N F    SEQ ID 7 Variants       F                                                          L                                     I                F                   L                F                   I          Location 1 2 3 4 5 6 7 8 9    NFYB-001 Peptide code V Y T T S Y Q Q I    SEQ ID 8 Variants       F                                                          L                                     F                F                   L                F                   F          Location 1 2 3 4 5 6 7 8 9    SMC4-001 Peptide code H Y K P T P L Y F    SEQ ID 9 Variants       F                                                          L                                     I                F                   L                F                   I          Location 1 2 3 4 5 6 7 8 9 10 UQCRB-001 Peptide code Y Y N A A G F N K L SEQ ID 10 Variants       F                                                             F                                     I             F                      F             F                      I       Location 1 2 3 4 5 6 7 8 9    PPAP2C-001 Peptide code A Y L V Y T D R L    SEQ ID 11 Variants       F                                                          F                                     I                F                   F                F                   I          Location 1 2 3 4 5 6 7 8 9    AVL9-001 Peptide code F Y I S P V N K L    SEQ ID 12 Variants       F                                                          F                                     I                F                   F                F                   I          Location 1 2 3 4 5 6 7 8 9    NUF2-001 Peptide code V Y G I R L E H F    SEQ ID 13 Variants       F                                                          L                                     I                F                   L                F                   I          Location 1 2 3 4 5 6 7 8 9    ABL1-001 Peptide code T Y G N L L D Y L    SEQ ID 14 Variants       F                                                          F                                     I                F                   F                F                   I          Location 1 2 3 4 5 6 7 8 9    MUC-006 Peptide code N Y E E T F P H I    SEQ ID 15 Variants       F                                                          F                                     L                F                   F                F                   L          Location 1 2 3 4 5 6 7 8 9    ASPM-001 Peptide code R Y L W A T V T I    SEQ ID 16 Variants       F                                                          F                                     L                F                   F                F                   L          Location 1 2 3 4 5 6 7 8 9    EPHA2-005 Peptide code V Y F S K S E Q L    SEQ ID 17 Variants       F                                                          F                                     I                F                   F                F                   I          Location 1 2 3 4 5 6 7 8 9    MMP3-001 Peptide code V F I F K G N Q F    SEQ ID 18 Variants       Y                                                          L                                     I                Y                   L                Y                   I          Location 1 2 3 4 5 6 7 8 9    NUF2-002 Peptide code R F L S G I I N F    SEQ ID 19 Variants       Y                                                          L                                     I                Y                   L                Y                   I          Location 1 2 3 4 5 6 7 8 9    PLK4-001 Peptide code Q Y A S R F V Q L    SEQ ID 20 Variants       F                                                          F                                     I                F                   F                F                   I          Location 1 2 3 4 5 6 7 8 9    ATAD2-002 Peptide code K Y L T V K D Y L    SEQ ID 21 Variants       F                                                          F                                     I                F                   F                F                   I          Location 1 2 3 4 5 6 7 8 9    COL12A1-001 Peptide code V Y N P T P N S L    SEQ ID 22 Variants       F                                                          F                                     I                F                   F                F                   I          Location 1 2 3 4 5 6 7 8 9    COL6A3-001 Peptide code S Y L Q A A N A L    SEQ ID 23 Variants       F                                                          F                                     I                F                   F                F                   I          Location 1 2 3 4 5 6 7 8 9    FANCI-001 Peptide code F Y Q P K I Q Q F    SEQ ID 24 Variants       F                                                          L                                     I                F                   L                F                   I          Location 1 2 3 4 5 6 7 8 9    RSP11-001 Peptide code Y Y K N I G L G F    SEQ ID 25 Variants       F                                                          L                                     I                F                   L                F                   I          Location 1 2 3 4 5 6 7 8 9    ATAD2-001 Peptide code A Y A I I K E E L    SEQ ID 26 Variants       F                                                          F                                     I                F                   F                F                   I          Location 1 2 3 4 5 6 7 8 9    ATAD2-003 Peptide code L Y P E V F E K F    SEQ ID 27 Variants       F                                                          L                                     I                F                   L                F                   I          Location 1 2 3 4 5 6 7 8 9 10 HSP90B1-001 Peptide code K Y N D T F W K E F SEQ ID 28 Variants       F                                                             L                                     I             F                      L             F                      I       Location 1 2 3 4 5 6 7 8 9 10 SIAH2-001 Peptide code V F D T A I A H L F SEQ ID 29 Variants       Y                                                             L                                     I             Y                      L             Y                      I       Location 1 2 3 4 5 6 7 8 9    SLC6A6-001 Peptide code V Y P N W A I G L    SEQ ID 30 Variants       F                                                          F                                     I                F                   F                F                   I          Location 1 2 3 4 5 6 7 8 9    IQGAP3-001 Peptide code V Y K V V G N L L    SEQ ID 31 Variants       F                                                          F                                     I                F                   F                F                   I          Location 1 2 3 4 5 6 7 8 9    ERBB3-001 Peptide code V Y I E K N D K L    SEQ ID 32 Variants       F                                                          F                                     I                F                   F                F                   I          Location 1 2 3 4 5 6 7 8 9 10 KIF2C-001 Peptide code I Y N G K L F D L L SEQ ID 33 Variants       F                                                             F                                     I             F                      F             F                      I       Location 1 2 3 4 5 6 7 8 9 10 CDC2-001 Peptide code L Y Q I L Q G I V F SEQ ID 1 Variants       F                                                             L                                     I             F                      L             F                      I       Location 1 2 3 4 5 6 7 8 9    ASPM-002 Peptide code S Y N P L W L R I    SEQ ID 2 Variants       F                                                          L                                     F                F                   L                F                   F          Location 1 2 3 4 5 6 7 8 9    UCHL5-001 Peptide code N Y L P F I M E L    SEQ ID 3 Variants       F                                                          F                                     I                F                   F                F                   I          Location 1 2 3 4 5 6 7 8 9    MET-006 Peptide code S Y I D V L P E F    SEQ ID 4 Variants       F                                                          L                                     I                F                   F                F                   I          Location 1 2 3 4 5 6 7 8 9    PROM-001 Peptide code S Y I I D P L N L    SEQ ID 5 Variants       F                                                          F                                     I                F                   F                F                   I          Location 1 2 3 4 5 6 7 8 9 10 MMP11-001 Peptide code V W S D V T P L T F SEQ ID 6 Variants       Y                                     F                                                             L                                     I             Y                      L             Y                      I             F                      L             F                      I       Location 1 2 3 4 5 6 7 8 9    MST1R-001 Peptide code N Y L L Y V S N F    SEQ ID 7 Variants       F                                                          L                                     I                F                   L                F                   I          Location 1 2 3 4 5 6 7 8 9    NFYB-001 Peptide code V Y T T S Y Q Q I    SEQ ID 8 Variants       F                                                          L                                     F                F                   L                F                   F          Location 1 2 3 4 5 6 7 8 9    SMC4-001 Peptide code H Y K P T P L Y F    SEQ ID 9 Variants       F                                                          L                                     I                F                   L                F                   I          Location 1 2 3 4 5 6 7 8 9 10 UQCRB-001 Peptide code Y Y N A A G F N K L SEQ ID 10 Variants       F                                                             F                                     I             F                      F             F                      I       Location 1 2 3 4 5 6 7 8 9    PPAP2C-001 Peptide code A Y L V Y T D R L    SEQ ID 11 Variants       F                                                          F                                     I                F                   F                F                   I          Location 1 2 3 4 5 6 7 8 9    AVL9-001 Peptide code F Y I S P V N K L    SEQ ID 12 Variants       F                                                          F                                     I                F                   F                F                   I          Location 1 2 3 4 5 6 7 8 9    NUF2-001 Peptide code V Y G I R L E H F    SEQ ID 13 Variants       F                                                          L                                     I                F                   L                F                   I          Location 1 2 3 4 5 6 7 8 9    ABL1-001 Peptide code T Y G N L L D Y L    SEQ ID 14 Variants       F                                                          F                                     I                F                   F                F                   I          Location 1 2 3 4 5 6 7 8 9    MUC-006 Peptide code N Y E E T F P H I    SEQ ID 15 Variants       F                                                          F                                     L                F                   F                F                   L          Location 1 2 3 4 5 6 7 8 9    ASPM-001 Peptide code R Y L W A T V T I    SEQ ID 16 Variants       F                                                          F                                     L                F                   F                F                   L          Location 1 2 3 4 5 6 7 8 9    EPHA2-005 Peptide code V Y F S K S E Q L    SEQ ID 17 Variants       F                                                          F                                     I                F                   F                F                   I          Location 1 2 3 4 5 6 7 8 9    MMP3-001 Peptide code V F I F K G N Q F    SEQ ID 18 Variants       Y                                                          L                                     I                Y                   L                Y                   I          Location 1 2 3 4 5 6 7 8 9    NUF2-002 Peptide code R F L S G I I N F    SEQ ID 19 Variants       Y                                                          L                                     I                Y                   L                Y                   I          Location 1 2 3 4 5 6 7 8 9    PLK4-001 Peptide code Q Y A S R F V Q L    SEQ ID 20 Variants       F                                                          F                                     I                F                   F                F                   I          Location 1 2 3 4 5 6 7 8 9    ATAD2-002 Peptide code K Y L T V K D Y L    SEQ ID 21 Variants       F                                                          F                                     I                F                   F                F                   I          Location 1 2 3 4 5 6 7 8 9    COL12A1-001 Peptide code V Y N P T P N S L    SEQ ID 22 Variants       F                                                          F                                     I                F                   F                F                   I          Location 1 2 3 4 5 6 7 8 9    COL6A3-001 Peptide code S Y L Q A A N A L    SEQ ID 23 Variants       F                                                          F                                     I                F                   F                F                   I          Location 1 2 3 4 5 6 7 8 9    FANCI-001 Peptide code F Y Q P K I Q Q F    SEQ ID 24 Variants       F                                                          L                                     I                F                   L                F                   I          Location 1 2 3 4 5 6 7 8 9    RSP11-001 Peptide code Y Y K N I G L G F    SEQ ID 25 Variants       F                                                          L                                     I                F                   L                F                   I          Location 1 2 3 4 5 6 7 8 9    ATAD2-001 Peptide code A Y A I I K E E L    SEQ ID 26 Variants       F                                                          F                                     I                F                   F                F                   I          Location 1 2 3 4 5 6 7 8 9    ATAD2-003 Peptide code L Y P E V F E K F    SEQ ID 27 Variants       F                                                          L                                     I                F                   L                F                   I          Location 1 2 3 4 5 6 7 8 9 10 HSP90B1-001 Peptide code K Y N D T F W K E F SEQ ID 28 Variants       F                                                             L                                     I             F                      L             F                      I       Location 1 2 3 4 5 6 7 8 9 10 SIAH2-001 Peptide code V F D T A I A H L F SEQ ID 29 Variants       Y                                                             L                                     I             Y                      L             Y                      I       Location 1 2 3 4 5 6 7 8 9    SLC6A6-001 Peptide code V Y P N W A I G L    SEQ ID 30 Variants       F                                                          F                                     I                F                   F                F                   I          Location 1 2 3 4 5 6 7 8 9    IQGAP3-001 Peptide code V Y K V V G N L L    SEQ ID 31 Variants       F                                                          F                                     I                F                   F                F                   I          Location 1 2 3 4 5 6 7 8 9    ERBB3-001 Peptide code V Y I E K N D K L    SEQ ID 32 Variants       F                                                          F                                     I                F                   F                F                   I          Location 1 2 3 4 5 6 7 8 9 10 KIF2C-001 Peptide code I Y N G K L F D L L SEQ ID 33 Variants       F                                                             F                                     I             F                      F             F                      I Longer peptides may also be suitable. MHC class I epitopes (usually 8 to 11 amino acids in length) may also result from peptide processing from longer peptides or proteins containing the actual epitope. Residues flanked by the actual epitope are preferably residues that, during processing, have little effect on the proteolytic cleavage required to expose the actual epitope. Accordingly, the present invention also proposes peptides and variants of MHC class I epitopes, wherein the total length of the peptide or antibody is 8 to 100, preferably 8 to 30, most preferably 8 to 14 (ie 8, 9, 10, 11, 12, 13, 14) amino acids. Of course, the peptides or variants of the invention can bind to human major histocompatibility complex (MHC) class I or II molecules. Binding of peptides or variants to MHC complexes can be tested using methods known in the art. In a particularly preferred embodiment of the invention, the peptide consists or consists essentially of amino acids according to SEQ ID NO: 1 to SEQ ID NO: 95. "Consisting essentially of" means a peptide of the invention which, in addition to being constituted according to any one of SEQ ID NO: 1 to SEQ ID NO: 95 or a variant thereof, also contains other N- and/or C-terminal extension of amino acids that do not necessarily form peptides that are epitopes of MHC molecules. However, these extended regions are important for the efficient introduction of the peptides of the present invention into cells. In one embodiment of the present invention, the peptide is a fusion protein containing 80 N-terminal amino acids of the HLA-DR antigen-related invariant chain (p33, hereinafter referred to as "Ii") from NCBI, GenBank Accession No. X00497, etc. In addition, the peptide or variant can be further modified to increase stability and/or bind to MHC molecules, thereby eliciting a stronger immune response. Such methods of optimization of peptide sequences are well known in the art and include, for example, the introduction of trans-peptide bonds and non-peptide bonds. In trans-peptide bond amino acids, the peptide (-CO-NH-) has no residues attached to it, but its peptide bond is reversed. Such retro-inverso peptidomimetics can be prepared by methods known in the art, eg, as described by Meziere et al. in J. Immunol. ((1997) J. Immunol. 159, 3230-3237) methods, incorporated herein by reference. This method involves the preparation of peptidomimetics that contain backbone (rather than side chain) alterations. A study by Meziere et al. (1997) showed that these analogous peptides facilitate MHC binding and helper T cell responses. Retro-inverse peptides with NH-CO bonds instead of CO-NH peptide bonds greatly improved hydrolysis resistance. Non-peptide bond is -CH₂ -NH, -CH₂ S-, -CH₂ CH₂ -, -CH=CH-, -COCH₂ -, -CH(OH)CH₂ -and-CH₂ SO-et al. U.S. Patent No. 4,897,445 proposes a non-peptide bond (-CH₂ -Non-solid phase synthesis of NH) involving polypeptides synthesized according to standard procedures and via aminoaldehydes and a NaCNBH-containing_{3 of} Non-peptide bonds synthesized by the interaction of amino acids. Peptides containing the above sequences can be synthesized with other chemical groups at their amino and/or carboxyl termini, thereby improving the stability, bioavailability, and/or affinity of the peptides. For example, hydrophobic groups such as benzyloxycarbonyl, danyl, or a t-butoxycarbonyl group can be added to the amino terminus of the peptide. Likewise, the acetyl or 9-fluorenylmethoxycarbonyl group may be located at the amino terminus of the peptide. In addition, hydrophobic groups, t-butoxycarbonyl groups or amino groups may all be added to the carboxy terminus of the peptide. In addition, all peptides of the present invention may be synthesized to alter their steric configuration. For example, it is possible to use the dextromer of one or more amino acid residues of these peptides, usually not the levorotid. Furthermore, at least one amino acid residue of the peptides of the present invention may be substituted with a well-known unnatural amino acid residue. Changes such as these may help to increase the stability, bioavailability and/or binding of the peptides of the invention. Likewise, the peptides or variants of the present invention may be chemically modified by the reaction of specific amino acids before or after synthesis of the peptide. Examples of such modifications are well known in the art and are outlined, for example, in "Chemical Reagents for Protein Modification" by R. Lundblad (3rd ed. CRC Press, 2005), incorporated herein by reference. Although the method of chemical modification of amino acids is not limited, it includes, but is not limited to, modification by the following methods: acylation, amidinoylation, lysine pyridoxylation, reductive alkylation, modification with 2,4,6- Trinitrobenzenesulfonic acid (TNBS) trinitrophenylated amino group, amino modification of carboxyl and sulfhydryl groups by oxidation of cysteine performic acid to sulfoalanine, formation of labile derivatives, and Other sulfhydryl compounds form mixed disulfide compounds, react with maleimide, carboxymethylation with iodoacetic acid or iodoacetamide, and methylated with cyanate at alkaline pH. In this regard, the skilled person refers to a broad range of methods related to chemical modification of proteins described in Chapter 15 of Current Protocols In Protein Science (Eds. Coligan et al. (John Wiley & Sons NY 1995-2000)). Briefly, arginine residues, etc., of modified proteins are often based on the reaction of ortho-dicarbonyl compounds such as benzaldehyde, 2,3-butanedione, and 1,2-ene diketone to form adducts. thing. Another example is the reaction of glyoxal with arginine residues. Cysteine can be modified without concomitant modification of nucleophilic sites such as lysine and histidine. Therefore, a large number of reagents are available for cysteine modification. Websites of companies such as Sigma-Aldrich (http://www.sigma-aldrich.com) contain information on specific reagents. Selective reduction of disulfide bonds in proteins is also common. Disulfide bonds can be formed and oxidized during thermal processing of biopharmaceuticals. Woodward's reagent K can be used to modify specific glutamic acid residues. N-(3-Dimethylaminopropyl)-N'-ethyl-carbodiimide can be used to form intramolecular crosslinks of lysine residues and glutamic acid residues. For example: Diethylpyrocarbonate is a reagent for modifying histidine residues in proteins. Histidine can also be modified with 4-hydroxy-2-nonenal. Reaction of lysine residues with other β-amino groups, for example, facilitates binding of peptides to the surface or cross-linking of proteins/peptides. Lysine poly is the attachment point of poly(ethylene) glycol and the major modification site for protein glycosylation. Methionine residues of proteins can be modified by iodoacetamide, bromoethylamine, chloramine T, and the like. Tetranitromethane and N-acetylimidazole can be used for modification of tyrosine residues. Crosslinking via dtyrosine can be accomplished by hydrogen peroxide/copper ions. Recent studies on tryptophan modification have used N-bromosuccinimide, 2-hydroxy-5-nitrobenzyl bromide, or 3-bromo-3-methyl-2-(2-nitrophenylthio)- 3H-Indole (BPNS-skatole). Successful modification of therapeutic proteins and polyethylene glycol-containing peptides tends to extend loop half-life when cross-linking of proteins with glutaraldehyde, polyethylene glycol diacrylate, and formaldehyde is used to formulate hydrogels. Chemical modification of allergens for immunotherapy is often achieved by carbamateylation of potassium cyanate. A peptide or variant, wherein the peptide is modified or contains non-peptide bonds, is preferably an embodiment of the present invention. In general, peptides and variants (containing at least peptide linkages between amino acid residues) can be synthesized using the solid-phase peptide synthesis Fmoc-polyamide model as disclosed in Lu et al. (1981) and the references listed here. Synthesize. The fluorenemethoxycarbonyl (Fmoc) group provides temporary protection of the N-amino group. Repeated cleavage was performed using a highly sensitive protecting group for this halide in 20% dimethyldimethazine in N,N-dimethylformamide. Due to their butyl ethers (in the case of serine threonine and tyrosine), butyl esters (in the case of glutamic acid and aspartic acid), tert-butoxycarbonyl derivatives (in the case of lysine and histidine), trityl derivatives (in the case of cysteine) and 4-methoxy-2,3,6-trimethylbenzenesulfonyl derivatives (in the case of refined amino acid), the side chain function may be protected. As long as glutamine and aspartamine are C-terminal residues, the side chain amino function protection used is by a 4,4'-dimethoxydiphenyl group. The solid phase support is based on a polydimethylacrylamide polymer, which consists of three monomers dimethylacrylamide (backbone monomer), bisacryloylethylenediamine (crosslinker) and N-acrylonosamine Methyl acid (functional agent) composition. The peptide-resin linker used was an acid-sensitive 4-hydroxymethylphenoxyacetic acid derivative. All amino acid derivatives were added as their preformed symmetrical anhydride derivatives, with the exception of asparagine and glutamine, which used reversed N,N-dicyclohexylcarbodiimide/1-hydroxybenzotrimine azole-mediated coupling procedure was added. All coupling and deprotection reactions were monitored using ninhydrin, nitrobenzenesulfonic acid or isotin test procedures. After the synthesis was complete, the peptide was cleaved from the resin support with the removal of side chain protecting groups using 95% trifluoroacetic acid containing a 50% scavenger mixture. Commonly used scavenger mixtures include ethanedithiol, phenol, anisole, and water, and the exact selection depends on the amino acid composition of the synthetic peptide. In addition, it is possible to synthesize peptides using a combination of solid-phase and liquid-phase methods (for example, see Bruckdorfer et al. Trifluoroacetic acid was removed by evaporation in vacuo followed by titration with diethyl ether bearing the crude peptide. Any scavenger mixture present was removed using a simple extraction procedure (which yielded peptides free of scavenger mixture after aqueous lyophilization). Peptide synthesis reagents are generally available from Calbiochem-Novabiochem (UK) plc (NG7 2QJ, UK). Purification can be carried out by any one or a combination of the following techniques, such as: recrystallization, size exclusion chromatography, ion exchange chromatography, hydrophobic interaction chromatography, and (usually) reverse phase high performance liquid chromatography (eg, using acetonitrile/ water gradient separation). Peptide analysis can be performed using the following methods: thin layer chromatography, electrophoresis, in particular, capillary electrophoresis, solid phase extraction (CSPE), reverse phase high performance liquid chromatography, amino acid analysis after acid hydrolysis, fast atom bombardment ( FAB) mass spectrometry and MALDI, ESI-Q-TOF mass spectrometry. In another aspect, the present invention provides a nucleic acid (eg, a polynucleotide) encoding the peptide or peptide variant of the present invention. Polynucleotides may be, for example, DNA, cDNA, PNA, CNA, RNA, or combinations thereof, which may be single- and/or double-stranded, or native or stable forms of polynucleotides (eg, with A polynucleotide of a phosphorothioate backbone) and may or may not contain introns as long as it encodes a peptide. Of course, polynucleotides can only encode peptides that incorporate natural peptide bonds and contain natural amino acid residues. In another aspect, the present invention provides an expression vector that can express a polypeptide according to the present invention. For ligating polynucleotides, various methods have been developed, especially for DNA, such as by supplementing the vector with ligatable ends. For example, complementary homopolymer tracks can be added to the DNA fragments, which are then inserted into the vector DNA. The vector and DNA fragments are then combined by hydrogen bonding of complementary homopolymer tails, thereby forming recombinant DNA molecules. Synthetic linkers containing one or more restriction sites provide an alternative method for ligating DNA fragments to vectors. Synthetic linkers containing various restriction endonucleases are commercially available through a variety of sources, including from International Biotechnologies Inc, New Haven, CN, USA. A desirable method of modification of the DNA encoding the polypeptides of the present invention is to use the polymerase chain reaction method employed by Saiki et al. (1988). This method can be used to introduce DNA into a suitable vector (eg, by designing suitable restriction sites), and can also be used to modify DNA by other useful methods known in the art. If a viral vector is used, a poxvirus vector or an adenovirus vector is preferred. The DNA (or RNA in the case of retroviral vectors) may then be expressed in a suitable host to produce a polypeptide containing the peptide or variant of the invention. Thus, the polypeptides of the present invention can be expressed and produced according to known techniques using DNA encoding the peptides or variants of the present invention, suitably modified by the methods described herein, to construct expression vectors, which are then used to transform suitable host cells . These methods include those disclosed in the following US Patents: 4,440,859; 4,530,901; 4,582,800; 4,677,063; 4,678,751; 4,704,362; 4,710,463; DNA (or, in the case of retroviral vectors, RNA) encoding a polypeptide containing a compound of the present invention may be added to a variety of other DNA sequences for introduction into a suitable host. Companion DNA will depend on the nature of the host, how the DNA was introduced into the host, and whether it needs to remain episomal or bind to each other. Generally, DNA can be attached to an expression vector (eg, a plasmid) in the proper orientation and in the correct expression reading frame. If necessary, the DNA may be linked to corresponding transcriptional and translational regulatory control nucleotide sequences recognized by the desired host, although such control functions are typically present in expression vectors. The vector is then introduced into the host by standard methods. In general, not all hosts will be transformed with the vector. Therefore, it is necessary to select transformed host cells. Selection methods include inserting into the expression vector a DNA sequence encoding a selectable attribute (eg, antibiotic resistance) in the transformed cell, with any necessary control elements. Alternatively, the gene with this selective property can be on another vector that is used to cooperatively transform the desired host cell. The host cells transformed with the recombinant DNAs of the present invention are then cultured under suitable conditions familiar to those skilled in the art described herein for a period of time sufficient to express the peptides which can then be recovered. There are many known expression systems, including bacteria (eg, E. coli and Bacillus subtilis), yeast (eg, yeast), filamentous fungi (eg, Aspergillus), plant cells, animal cells, and insect cells. The system may preferably be mammalian cells, such as CHO cells from the ATCC Cell Biology Collection. Typical mammalian cell constitutive expression vector plasmids include CMV or SV40 promoters with a suitable poly A tail and resistance markers (eg, neomycin). An example is pSVL obtained from Pharmacia Corporation (Piscataway, NJ, USA). An example of an inducible mammalian expression vector is pMSG, also available from Pharmacia. Useful yeast plasmid vectors are pRS403-406 and pRS413-416, generally available from Stratagene Cloning Systems (La Jolla, CA 92037, USA). Plasmids pRS403, pRS404, pRS405 and pRS406 are yeast integrating plasmids (YIp) with insertions of the yeast selectable markers HIS3, TRP1, LEU2 and URA3. The pRS413-416 plasmid is a yeast centromeric plasmid (Ycp). CMV promoter-based vectors (eg, from Sigma-Aldrich) provide transient or stable expression, cytoplasmic expression or secretion, as well as FLAG, 3xFLAG, c-myc or N-terminal or C-terminal labeling in different compositions of MATN. These fusion proteins can be used for detection, purification and analysis of recombinant proteins. Dual-label fusion provides flexibility for detection. The robust human cytomegalovirus (CMV) promoter regulatory region enables constitutive protein expression levels up to 1 mg/L in COS cells. For weaker cell lines, protein levels are generally below 0.1 mg/L. The emergence of the SV40 origin of replication will lead to high levels of DNA replication in SV40 replication-compatible COS cells. For example, a CMV vector may contain the pMB1 (derivative of pBR322) origin of replication in bacterial cells, the calcium-lactamase gene for ampicillin resistance selection in bacteria, the origin of hGH polyA and fl. A vector containing a preproinsulin leader (PPT) sequence can be used to direct secretion of the FLAG fusion protein into the medium in which purification is performed using an anti-FLAG antibody, resin and plate. Other vectors and expression systems for use with various host cells are well known in the art. The present invention also relates to a host cell transformed with the polynucleotide vector of the present invention. Host cells can be prokaryotic cells or eukaryotic cells. In some cases, bacterial cells are preferably prokaryotic host cells, typically E. coli strains, eg, E. coli strains DH5 (obtained from Bethesda Research Laboratories, MD, USA) and RR1 (obtained from the American Type Culture Collection ( ATCC, Rockville, MD, USA), obtained with ATCC No. 31343). Preferred eukaryotic host cells include yeast, insect and mammalian cells, preferably vertebrate cells such as mouse, rat, monkey or human fibroblasts and cells in colon cancer cell lines. Yeast host cells include YPH499, YPH500 and YPH501, generally available from Stratagene Cloning Systems (La Jolla, CA 92037, USA). Preferred mammalian host cells include Chinese hamster ovary (CHO) cells as CCL61 cells in ATCC, NIH Swiss mouse embryo cells NIH/3T3 as CRL 1658 cells in ATCC, monkey kidney-derived COS-1 cells as CRL in ATCC 1650 cells and 293 cells of human embryonic kidney cells. The preferred insect cells are Sf9 cells, which can be transfected with baculovirus expression vectors. An outline for selecting suitable host cells for expression can be found in textbooks (Paulina Balbás and Argelia Lorence "Methods in Molecular Biology Recombinant Gene Expression, Reviews and Protocols" Part One, Second Edition, ISBN 978-1-58829-262-9) and found in other documents known to those skilled in the art. Transformation of suitable host cells containing the DNA constructs of the present invention can be accomplished using well-known methods, generally depending on the type of vector used. For transformation of prokaryotic host cells, see, e.g., Cohen et al. (1972) in Proc. Natl. Acad. Sci. USA 1972, 69, 2110 and "Molecular Cloning, A Laboratory Manual" by Sambrook et al. (1989). 》 Method used in Cold Spring Harbor Laboratory, Cold Spring Harbor, NY. Transformation of yeast cells is described in Sherman et al. (1986) in Methods In Yeast Genetics, A Laboratory Manual, Cold Spring Harbor, NY. The method described in Beggs (1978) Nature 275, 104-109 is also useful. For vertebrate cells, reagents and the like for transfection of these cells, eg, calcium phosphate and DEAE-dextran or liposomal formulations, are available from Stratagene Cloning Systems or Life Technologies (Gaithersburg, MD 20877, USA). Electroporation can also be used to transform and/or transfect cells and is a method well known in the art for transforming yeast cells, bacterial cells, insect cells and vertebrate cells. Successfully transformed cells (ie, cells containing the DNA constructs of the present invention) can be identified by well-known methods such as PCR. Alternatively, proteins present in the supernatant can be detected using antibodies. It will be appreciated that certain host cells of the present invention are used to prepare the peptides of the present invention, such as bacterial cells, yeast cells and insect cells. However, other host cells may be useful for some treatments. For example, antigen-presenting cells (eg, dendritic cells) can be used to express the peptides of the invention so that they can be loaded into the corresponding MHC molecules. Accordingly, the present invention proposes a host cell containing the nucleic acid or expression vector of the present invention. In a preferred embodiment, the host cells are antigen-presenting cells, especially dendritic cells or antigen-presenting cells. Currently, APCs containing recombinant fusion proteins containing prostate acid phosphatase (PAP) are being studied for the treatment of prostate cancer (Sipuleucel-T) (Rini et al. 67-74; Small et al. 3089 -94). In another aspect, the present invention provides a method of formulating a peptide and variants thereof, the method comprising culturing a host cell and isolating the peptide from the host cell or its culture medium. In another embodiment, the peptides, nucleic acids or expression vectors of the present invention are used in medicine. For example, peptides or variants thereof can be prepared as intravenous (i.v.) injections, subcutaneous (s.c.) injections, intradermal (i.d.) injections, intraperitoneal (i.p.) injections, intramuscular (i.m.) injections. Preferred methods of peptide injection include s.c., i.d., i.p., i.m. and i.v. injections. Preferred methods of DNA injection are i.d., i.m., s.c., i.p. and i.v. injections. For example, 50 µg to 1.5 mg, preferably 125 µg to 500 µg of peptide or DNA is administered, depending on the specific peptide or DNA. The above dose ranges have been used successfully in previous trials (Brunsvig et al. 1553-64; Staehler et al.). Another aspect of the invention includes a method of producing primed T cells in vitro, the method comprising in vitro ligating T cells to antigen-loaded human MHC molecules that are expressed on the surface of suitable antigen-presenting cells for a sufficient period of time T cells are thereby primed in an antigen-specific manner, wherein the antigen is a peptide according to the present invention. Preferably, a sufficient amount of antigen is used with antigen presenting cells. Preferably, the TAP peptide transporter in mammalian cells is deficient or reduced in level or function. Suitable cells lacking the TAP peptide transporter include T2, RMA-S and Drosophila cells. TAP is a transporter associated with antigen processing. Human peptide loading deficient cell line T2 belongs to American Type Culture Collection (ATCC, 12301 Parklawn Drive, Rockville, Maryland 20852, USA) catalog number CRL1992; Drosophila cell line Schneider 2 strain belongs to ATCC catalog CRL 19863; mouse RMA -S cell line described by Karre et al in 1985. Preferably, the host cells do not substantially express MHC class I molecules prior to transfection. Stimulatory factor cells also preferably express molecules that are important for T cell costimulatory signaling, eg, any of B7.1, B7.2, ICAM-1, and LFA3. Nucleic acid sequences for a large number of MHC class I molecules and costimulatory molecules are publicly available from the GenBank and EMBL databases. When the MHC class I epitope is used as an antigen, T cells are CD8 positive CTL. If antigen-presenting cells are transfected to express such epitopes, preferred cells include an expression vector capable of expressing the amino acid sequences of peptides comprising SEQ ID NO: 1 to SEQ ID NO: 95 or variants thereof. Several other methods can be used to generate CTLs in vitro. For example, the method described by Peoples et al. (1995) and the method of Kawakami et al. (1992) using autologous tumor-infiltrating lymphocytes can be used to generate CTL. Plebanski et al. (1995) used autologous peripheral blood lymphocytes (PLB) to generate CTLs. Jochmus et al. (1997) describe the production of autologous CTLs by pulsed dendritic cells with peptides or polypeptides or by infection with recombinant viruses. Hill et al. (1995) and Jerome et al. (1993) used B cells to make autologous CTLs. In addition, macrophages pulsed with peptides or polypeptides or infected with recombinant viruses can be used to formulate autologous CTLs. Walter et al. in 2003 described in vitro priming of T cells by using artificial antigen presenting cells (aAPCs), which is also a suitable method for generating T cells acting on selected peptides. In this study, aAPCs were generated by coupling preformed MHC:peptide complexes to polystyrene particles (microspheres) according to a biotin:streptomycin biochemical approach. This system enables precise modulation of MHC density on aAPCs, which allows selective elicitation of high- or low-affinity antigen-specific T cell responses in blood samples. In addition to the MHC:peptide complexes, aAPCs should also carry other proteins with co-stimulatory activity, such as anti-CD28 antibodies coupled to the surface. Furthermore, such aAPC-based systems often require the addition of appropriate soluble factors, eg, cytokines such as interleukin-12. T cells can also be generated from allogeneic cells, a method is described in detail in WO 97/26328, incorporated herein by reference. For example, in addition to Drosophila cells and T2 cells, other cells can also be used to present peptides, such as CHO cells, baculovirus-infected insect cells, bacteria, yeast, vaccinia-infected target cells. In addition, plant viruses can also be used (see, eg, Porta et al. (1994) describing the development of cowpea mosaic virus as a high-yield system for the presentation of foreign peptides. Activated T cells are directed against the peptides of the present invention, facilitating therapy. Therefore, another aspect of the present invention proposes priming T cells produced by the aforementioned method of the present invention. Primer T cells prepared as described above will selectively recognize cells that abnormally express a polypeptide comprising the amino acid sequence of SEQ ID NO: 1 to 95. Preferably, the T cell recognizes the cell by interacting (eg, binding) to its TCR containing the HLA/peptide complex. T cells are useful in methods for killing target cells of patients, whose target cells abnormally express the polypeptides comprising the amino acid sequences of the present invention. Such patients are administered an effective amount of priming T cells. T cells administered to a patient may be derived from the patient and primed as described above (ie, they are autologous T cells). Alternatively, the T cells were not derived from the patient, but from another person. Of course, it is preferred that the donor is a healthy human. The inventors use a "healthy individual" to mean a person who is generally in good health, preferably with a competent immune system, more preferably free of any disease that can be readily tested or detected. According to the present invention, the in vivo target cells of CD8-positive T cells may be tumor cells (sometimes expressing MHC class I antigens) and/or stromal cells (tumor cells) surrounding the tumor (sometimes expressing MHC class I antigens; (Dengjel et al. 4163-70)). The T cells of the present invention can be used as active ingredients in therapeutic compositions. Therefore, the present invention also provides a method for killing target cells of a patient, wherein the target cells of the patient abnormally express the polypeptide containing the amino acid sequence of the present invention, and the method comprises administering the above-mentioned effective amount of T cells to the patient. "Aberrantly expressed" as used by the inventors also means that the polypeptide is overexpressed compared to normal expression levels, or that the gene is not expressed in the tumor-derived tissue, but is expressed in the tumor. "Overexpression" means that the polypeptide level is at least 1.2-fold higher than in normal tissue; preferably at least 2-fold, more preferably at least 5- or 10-fold higher than in normal tissue. T cells can be produced by methods known in the art (eg, methods described above). T cell adoptive transfer protocols are well known in the art and can be found in the following references, for example: (Dudley et al. 850-54; Dudley et al. 2346-57; Rosenberg et al. 889-97; Rosenberg et al. al. 1676-80; Yee et al. 16168-73); reviews (Gattinoni et al. 383-93) and (Morgan et al.). Any of the molecules of the present invention (ie, peptides, nucleic acids, expression vectors, cells, initiating CTLs, T cell receptors, or encoding nucleic acids) are useful in the treatment of diseases characterized by cells evading the blow of an immune response. Thus, any molecule of the present invention can be used as a medicament or for the manufacture of a medicament. This molecule can be used alone or in combination with other molecules of the invention or known molecules. The agent described in the present invention is preferably a vaccine. The vaccine can be administered directly to the affected organ of the patient, administered systemically by i.d., i.m., s.c., i.p. and i.v. ), or in vitro for a subset of cells from immune cells from a patient (the cells are then re-administered to the patient). If the nucleic acid is injected into cells in vitro, it may be beneficial to transfect the cells to co-express immunostimulatory cytokines (eg, interleukin-2). The peptides can be administered entirely alone, or in combination with immunostimulatory adjuvants (see below), or in combination with immunostimulatory cytokines, or in a suitable delivery system (eg, liposomes). The peptide can also be conjugated to a suitable carrier such as keyhole limpet hemocyanin (KLH) or manna (see WO 95/18145 and Longenecker 1993). The peptide may also be labeled, or may be a fusion protein or hybrid molecule. The peptides of the given peptide sequences of the present invention are expected to stimulate CD4 or CD8 T cells. However, CD8 CTL stimulation was more effective when CD4 T helper cells were present. Thus, for MHC class I epitopes that stimulate CD8 CTL, a fusion partner or fragment of a hybrid molecule provides the appropriate epitope to stimulate CD4 positive T cells. CD4- and CD8 stimulating epitopes are well known in the art and include epitopes identified in the present invention. In one aspect, the vaccine comprises at least one peptide set forth in SEQ ID NOs: 1 to 33 and at least one other peptide, preferably 2 to 50, more preferably 2 to 25, still more preferably 2 to 15, most preferably be 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 peptides. Peptides may be derived from one or more specific TAAs and may bind to MHC class I molecules. The polynucleotide can be in substantially purified form, or it can be coated on a carrier or delivery system. Nucleic acids may be DNA, cDNA, PNA, CNA, RNA, or combinations thereof. Methods for the design and introduction of such nucleic acids are well known in the art. For example, it is outlined in the literature (Pascolo et al. 117-22). Polynucleotide vaccines are readily prepared, but the mode of action of these vectors to induce immune responses is not fully understood. Suitable vectors and delivery systems include viral DNA and/or RNA, such as systems based on adenovirus, vaccinia virus, retrovirus, herpes virus, adeno-associated virus, or mixed viruses containing more than one viral element. Non-viral delivery systems, including cationic liposomes and cationic polymers, are systems well known in the art for DNA delivery. Physical delivery systems, such as via a "gene gun", may also be used. The peptide or nucleic acid-encoded peptide can be a fusion protein, eg, containing an epitope that stimulates T cells to perform the CDRs described above. The agents of the present invention may also include one or more adjuvants. Adjuvants are those that nonspecifically enhance or enhance the immune response (e.g., via CTL and helper T(T)._H ) cell-mediated immune response to an antigen and is therefore considered useful for the agents of the invention. Suitable adjuvants include, but are not limited to, 1018ISS, aluminum salts, Amplivax®, AS15, BCG, CP-870,893, CpG7909, CyaA, dSLIM, flagellin or flagellin-derived TLR5 ligand, FLT3 ligand, GM-CSF , IC30, IC31, Imiquimod (ALDARA®), resiquimod, ImuFact IMP321, Interleukin IL-2, IL-13, IL-21, Interferon alpha or beta, or their polyethylene glycol derivatives, IS Patch, ISS, ISCOMATRIX, ISCOMs, JuvImmune, LipoVac, MALP2, MF59, Monophosphoric Acid A, Montanide IMS 1312, Montanide ISA 206, Montanide ISA 50V, Montanide ISA-51, Oil-in-Water and Water-in-Oil Emulsion, OK-432, OM-174, OM-197-MP-EC, ONTAK, OspA, PepTel® vector system, based on polylactide complex glycolide [PLG] and dextran microparticles, recombinant human lactoferrin SRL172, Viral particles and other virus-like particles, YF-17D, VEGF trap, R848, β-glucan, Pam3Cys, Aquila's QS21 stimulator derived from saponins, mycobacterial extracts, and bacterial cell wall synthesis mimics, and Other proprietary adjuvants such as Ribi's Detox, Quil or Superfos. Adjuvants such as Freund's adjuvant or GM-CSF are preferred. Some dendritic cell-specific immune adjuvants (such as MF59) and methods for their preparation have been described previously (Allison and Krummel 932-33). Cytokines can also be used. Several cytokines directly affect the migration of dendritic cells to lymphoid tissues (eg, TNF-) and accelerate the maturation of dendritic cells into potent antigen-presenting cells of T lymphocytes (eg, GM-CSF, IL-1, and IL-4). [ Gabrilovich 1996]. CpG immunostimulatory oligonucleotides have been reported to enhance the effect of adjuvants in vaccines. Without being bound by theory, CpG oligonucleotides act by priming the innate (non-adaptive) immune system through Toll-like receptors (TLRs), primarily TLR9. CpG-triggered TLR9 activation enhances antigen-specific humoral and cellular responses to a variety of antigens, including peptide or protein antigens, live or killed viruses, dendritic cell vaccines, autologous cell vaccines, and prophylactic and polysaccharide conjugates in therapeutic vaccines. More importantly, it enhances dendritic cell maturation and differentiation, leading to T_H1 Enhanced activation of cells and enhanced cytotoxic T lymphocyte (CTL) production, even in the absence of CD4 T cell specification. Even the presence of vaccine adjuvants maintains TLR9 activation-induced T_H1 offset, these adjuvants such as: normal promoting T_H2 Offset alum or incomplete Freund's adjuvant (IFA). CpG oligonucleotides exhibit stronger adjuvant activity when prepared or co-administered with other adjuvants or formulations such as microparticles, nanoparticles, lipid emulsions, or similar formulations, which are less effective when the antigen is relatively weak It is especially necessary to induce a strong response. They also accelerated immune responses, reducing antigen doses by about two orders of magnitude, and in some experiments produced similar antibody responses to full-dose vaccines without CpG (Krieg 471-84). US Patent No. 6,406,705 B1 describes the combined use of CpG oligonucleotides, non-nucleic acid adjuvants, and antigens to induce antigen-specific immune responses. A CpGTLR9 antagonist is dSLIM (double stem ring immunomodulator) from Mologen (Berlin, Germany), which is a preferred component of the pharmaceutical composition of the present invention. Other eg TLR binding molecules, eg RNA binding TLR7, TLR8 and/or TLR9 may also be used. Examples of other useful adjuvants include, but are not limited to, chemically modified CpGs (eg, CpR, Idera), dsRNA mimetics, eg, Poly(I:C) and derivatives thereof (eg: AmpliGen®, Hiltonol®, Polymeric -(ICLC), poly(IC-R), poly(I:C12U)), non-CpG bacterial DNA or RNA and immunologically active small molecules and antibodies such as: cyclophosphamide, sunitinib, Bevacizumab, Celebrex, NCX-4016, sildenafil, tadalafil, vardenafil, sorafenib, temozolomide, temsirolimus, XL-999, CP-547632, pazopanib, VEGF Trap, ZD2171, AZD2171, anti-CTLA4, other antibodies targeting major structures of the immune system (eg, anti-CD40, anti-TGFβ, anti-TNFα receptors) and SC58175, all of which may have therapeutic effects and/or act as an adjuvant. A skilled artisan can readily determine the amounts and concentrations of adjuvants and additives useful in the present invention without undue undue experimentation. Preferred adjuvants are imiquimod, resiquimod, GM-CSF, cyclophosphamide, sunitinib, bevacizumab, interferon-alpha, CpG oligonucleotides and derivatives, poly(I:C) and derivatives, RNA, sildenafil, and microparticle preparations or viral particles of PLG. In a preferred embodiment of the pharmaceutical composition of the present invention, the adjuvant is selected from colony-stimulating factor-containing preparations, such as granulocyte-macrophage colony-stimulating factor (GM-CSF, sagrastim), imiquimod, resiquimod and Interferon-alpha. In a preferred embodiment of the pharmaceutical composition of the present invention, the adjuvant is selected from colony-stimulating factor-containing preparations, such as granulocyte-macrophage colony-stimulating factor (GM-CSF, sagrastim), imiquimod and resimiquimod. In a preferred embodiment of the pharmaceutical composition of the present invention, the adjuvant is imiquimod or resiquimod. This combination drug is used for parenteral injection, such as subcutaneous, intradermal, intramuscular injection, and can also be taken orally. For this purpose, peptides and other selective molecules are dissolved or suspended in a pharmaceutically acceptable carrier, preferably an aqueous carrier. In addition, the composition may contain adjuvants such as: buffers, binders, shock agents, diluents, fragrances, lubricants, and the like. These peptides can also be used in combination with immunostimulatory substances such as cytokines. Further excipients that can be used in such compositions are known from, among others, Handbook of Pharmaceutical Excipients by A. Kibbe (3rd Edition, 2000, American Medical Association and Pharmaceutical Press). This combination drug can be used to stop, prevent and/or treat adenoma or cancerous disease. Example formulations are in EP2113253. The present invention proposes a medicament that is beneficial for the treatment of cancer, especially gastric cancer, renal cell carcinoma, colon cancer, non-small cell lung cancer, adenocarcinoma, prostate cancer, benign tumor and malignant melanoma. A kit of the present invention also includes: (a) a container containing the pharmaceutical composition described above in the form of a solution or lyophilized powder; (b) an optional second container containing the diluent or reconstituted solution in the lyophilized powder dosage form; and (c) Optionally, instructions for (i) using the solution or (ii) reconstituting and/or using the lyophilized powder dosage form. The kit further includes one or more of (iii) buffers, (iv) diluents, (v) filtrates, (vi) needles, or (v) syringes. The container is preferably a bottle, vial, syringe or test tube; it can also be a multipurpose container. The pharmaceutical combination is preferably a lyophilized powder. The kits of the present invention preferably contain a lyophilized formulation in a suitable container along with instructions for reconstitution and/or use. Suitable containers include, for example, bottles, vials (eg, dual-chamber vials), syringes (eg, dual-chamber syringes), and test tubes. The container may be made of various materials, such as glass or plastic. Preferably, the kit and/or container has instructions for reconstitution and/or use. For example, the label may indicate that the lyophilized dosage form is reconstituted to the above peptide concentrations. The label may further indicate that the formulation is for subcutaneous injection. The container in which the formulation is stored may use a multi-purpose vial, allowing repeated administration (eg, 2-6 times) of the reconstituted dosage form. The kit may further include a second container containing a suitable diluent, such as sodium bicarbonate solution. After mixing the diluent and the lyophilized formulation, the final peptide concentration in the reconstituted formulation is preferably at least 0.15 mg/mL/peptide (=75 g of peptide) and not more than 3 mg/mL/peptide (= 1500 g of peptidic). The kit may also include other materials desirable from a commercial and user standpoint, including other buffers, diluents, filtrates, needles, syringes, and package inserts with instructions for use. The kits of the present invention may have a single container containing the pharmaceutical composition formulation of the present invention, which may or may not have other ingredients (eg, other compounds or pharmaceutical compositions thereof), or Each ingredient has its own container. Preferably, the kits of the present invention comprise one formulation of the present invention, packaged with a second compound (eg, an adjuvant (eg, GM-CSF), a chemotherapeutic drug, a natural product, a hormone or antagonist, an anti-angiogenic agent, or inhibitors, apoptosis inducers or chelators) or their pharmaceutical compositions in combination. The components of the kit may be pre-complexed or each component may be placed in a separate distinct container prior to administration to the patient. The components of the kit may be one or more solutions, preferably aqueous solutions, more preferably sterile aqueous solutions. The components of the kit can also be in solid form, which can be converted to liquid after adding a suitable solvent, preferably in a different container. The container of the treatment kit may be a vial, test tube, flask, bottle, syringe, or any other means of holding solids or liquids. Often, when there is more than one ingredient, the kit will contain a second vial or other container to allow for individual dosing. The kit may also contain another container for medicinal liquids. Preferably, the treatment kit will contain a device (eg, one or more needles, syringes, eye droppers, pipettes, etc.) that enables the medicament of the invention (the composition of the kit) to be injected. The pharmaceutical formulations of the present invention are suitable for peptide administration by any acceptable route, such as oral (enteral), intranasal, intraocular, subcutaneous, intradermal, intramuscular, intravenous or transdermal administration. Subcutaneous administration is preferred, and intradermal administration is most preferred, but can also be administered by infusion pump. Since the peptides of the present invention derived from MST1R, UCHL5, SMC4, NFYB, PPAP2C, AVL9, UQCRB and MUC6 are isolated from gastric cancer, the agent of the present invention is preferably used for the treatment of gastric cancer. The following examples, which describe preferred embodiments, will illustrate (but not limit) the invention. All references are incorporated herein by reference in their entirety for the purposes of this disclosure.Example Example 1: Recognition of tumor-associated peptides presented on the cell surface tissue sample Patient tumor tissues were provided by Kyoto Prefectural University of Medicine (KPUM), Osaka, Japan, and Osaka City University Graduate School of Medicine (OCU), Osaka, Japan. All patients obtained written informed consent before surgery. Tissues were cold-shocked with liquid nitrogen immediately after surgery and stored at -80°C prior to isolation of TUMAPs. Isolation of HLA peptides from tissue samples Cold shock was obtained by immunoprecipitation of solid tissues using HLA-A, HLA-B, HLA-C specific antibody W6/32, CNBr-activated sepharose, acid treatment and ultrafiltration according to the protocol with slight modifications HLA peptide library of tissue samples (Falk, K.1991; Seeger, F.H.T1999). method The obtained HLA peptide library was separated by reversed-phase chromatography (Acquity UPLC system, Waters) according to its hydrophobicity, and the eluted peptides were analyzed by LTQ-Orbitrap hybrid mass spectrometer (ThermoElectron) equipped with an electrospray source. The peptide library was loaded directly into an analytical fused silica microcapillary column (75 µm id x 250 mm) packed with 1.7 µm C18 reversed-phase material (Waters) at an applied flow rate of 400 nL per minute. The peptides were then separated using a two-step 180-minute binary gradient in solvent B at a flow rate of 300 nL per minute at concentrations ranging from 10% to 33%. The gradient consisted of solvent A (0.1% formic acid in water) and solvent B (0.1% formic acid in acetonitrile). Gold-coated glass capillaries (PicoTip, New Objective) were used for introduction into the nanoliter electrospray source. The LTQ-Orbitrap mass spectrometer was operated in data-dependent mode using the top 5 (TOP5) strategy. Briefly, a scan cycle (R = 30 000) was started in the orbitrap with full scans at high precision quality, followed by MS/MS in the orbitrap for the 5 most abundant precursor ions using dynamic exclusion of previously selected ions Scan (R=7500). Tandem mass spectra were interpreted with SEQUEST and another manual controller. The resulting fragmentation patterns of natural peptides were compared to those of a synthetic reference peptide of the same sequence to ensure the identified peptide sequence. Figure 1 shows a typical spectrum of the MHC class I-related peptide CDC2-001 obtained from tumor tissue and its elution profile in the UPLC system. Example 2: Expression profile of the gene encoding the peptide of the present invention Not all peptides identified as being presented on the surface of tumor cells by MHC molecules are suitable for use in immunotherapy because most of these peptides are derived from normal cellular proteins expressed by many types of cells. Only a small fraction of these peptides are tumor-associated and may be able to induce T cells with high specificity for recognition of the tumor of origin. To identify these peptides and minimize the risk of autoimmunity induced by vaccination with these peptides, the inventors primarily employed peptides obtained from proteins overexpressed on tumor cells compared to most normal tissues. The ideal peptide is derived from a protein unique to the tumor and not present in other tissues. To identify peptides produced by genes with similar expression profiles to ideal genes, the identified peptides are assigned to proteins and genes, respectively, from which genes are obtained and expression profiles of these genes are generated. RNA source and preparation Surgically resected tissue specimens were provided by two different clinical centers (see Example 1) after obtaining written informed consent from each patient. Tumor tissue samples were snap-frozen in liquid nitrogen immediately after surgery and then homogenized with a pestle and mortar in liquid nitrogen. Total RNA was prepared from these samples using TRI reagent (Ambion, Darmstadt, Germany) followed by RNeasy (QIAGEN, Hilden, Germany) cleanup; both methods were performed according to the manufacturer's protocol. Total RNA in healthy human tissue was obtained commercially (Ambion, Huntingdon, UK; Clontech, Heidelberg, Germany; Stratagene, Amsterdam, The Netherlands; BioChain, Hayward, CA, USA). The RNAs of several individuals (2 to 123 individuals) were mixed so that each individual's RNA was equally weighted. Leukocytes were isolated from blood samples of 4 healthy volunteers. The quality and quantity of all RNA samples were assessed on an Agilent 2100 Bioanalyzer analyzer (Agilent, Waldbronn, Germany) using the RNA6000 Pico LabChip Kit (Agilent). Microarray experiments All tumor and normal tissue RNA samples were analyzed for gene expression using Affymetrix Human Genome (HG) U133A or HG-U133 Plus 2.0 Affymetrix Oligonucleotide Chips (Affymetrix Corporation, Santa Clara, CA, USA). All steps were performed according to the Affymetrix manual. Briefly, double-stranded cDNA was synthesized from 5-8 μg RNA using SuperScript RTII (Invitrogen) and oligo-dT-T7 primers (MWG Biotech, Ebersberg, Germany) as described in the manual. The U133A assay was performed with the BioArray High YieldRNA Transcript Labelling Kit (ENZO Diagnostics, Farmingdale, NY, USA) or the U133 Plus 2.0 assay with the GeneChip IVT Labelling Kit (Affymetrix), followed by streptavidin-phycoerythrin and biotinylation In vitro transcription was accomplished by fragmentation, hybridization and staining with anti-streptomycin antibody (Molecular Probes, Leiden, The Netherlands). Images were scanned with an Agilent 2500A GeneArray Scanner (U133A) or Affymetrix Gene-Chip Scanner 3000 (U133 Plus 2.0) and data were analyzed with GCOS software (Affymetrix) with all parameters default settings. For normalization, 100 housekeeping genes provided by Affymetrix were used. The relative expression value was calculated using the signal log ratio given by the software, and the value of normal kidney tissue samples was arbitrarily set to 1.0. The expression profile of the source gene of the present invention highly overexpressed in gastric cancer is shown in FIG. 2 . Example 3: In vitro immunogenicity of IMA941MHC-class I presenting peptide To obtain information on the immunogenicity of TUMAPs of the present invention, we used Walter, S, Herrgen, L, Schoor, O, Jung, G, Wernet, D, Buhring, HJ, Rammensee, HG and Stevanovic, S et al. Studies were conducted in 2003 on the widely accepted in vitro stimulation platform described in Cutting edge: predetermined avidity of humanCD8T cells expanded on calibratedMHC/anti-CD28-coated microspheres, J. Immunol., 171, 4974-4978. In this way, all 32 HLA-A*2402-restricted TUMAPs of the present invention showed immunogenicity, indicating that these peptides are T cell epitopes against human CD8+ precursor T cells (Table 4). In vitro priming of CD8+ T cells For in vitro stimulation with artificial antigen-presenting cells (aAPCs) loaded with peptide-MHC complexes (pMHCs) and anti-CD28 antibodies, we first obtained fresh HLA-A*24 products from healthy donors after leukopenia from the Tuebingen blood bank CD8 T cells were isolated. CD8 T cells were then enriched directly with the leukapheresis product, or PBMCs (peripheral blood mononuclear cells) were first isolated using standard gradient separation media (PAA, Cölbe, Germany). The isolated CD8 lymphocytes or PBMC were cultured in T cell culture medium (TCM) containing RPMI-Glutamax (Invitrogen, Karlsruhe, Germany) supplemented with 10% heat-inactivated human AB serum (PAN-Biotech, Aidenbach) before use. , Germany), 100 U/ml penicillin/100 µg/ml streptomycin (Cambrex, Cologne, Germany), 1 mM sodium pyruvate (CC Pro, Oberdorla, Germany), and 20 µg/ml gentamicin (Cambrex, Germany) company). At this step, 2.5 ng/ml IL-7 (PromoCell, Heidelberg, Germany) and 10 U/ml IL-2 (Novartis Pharma, Nürnberg, Germany) were also added to TCM. CD8+ lymphocytes were isolated by positive selection using MicroBeads (Miltenyi Biotec, Bergisch-Gladbach, Germany). Generation of pMHC/anti-CD28 coated beads, stimulation of T cells and readout methods were as previously described (Walter et al. 4974-78) with minor modifications. Briefly, biotinylated peptide-loaded recombinant HLA-A*2402 molecules lacking the transmembrane domain and biotinylated at the carboxy terminus of the heavy chain were prepared. Purified co-stimulatory mouse IgG2a anti-human CD28 antibody 9.3 (Jung, Ledbetter, and Muller-Eberhard 4611-15) was prepared using N-hydroxysuccinimidyl biotin as recommended by the manufacturer (Perbio, Bonn, Germany). Pigmentation treatment. The beads used were 5.6 µm large streptavidin-coated polystyrene particles (Bangs Laboratories, IL, USA). The pMHCs used as controls were A*0201/MLA-001 (peptide ELAGIGILTV modified from Melan-A/MART-1) and A*0201/DDX5-001 (YLLPAIVHI obtained from DDX5), respectively. 800.000 beads/200 µl coated in 96-well plate in the presence of 600 ng biotin anti-CD28 + 200 ng related biotin pMHC (high density beads). Co-culture 1 × 10 in 200 µl TCM containing 5 ng/ml IL-12 (PromoCell) at 37°C⁶ CD8+ T cells with 2 × 10⁵ Wash the coated beads for 3 to 4 days to initiate stimulation in 96-well plates. Afterwards, half of the medium was exchanged with fresh TCM supplemented with 80 U/ml IL-2 and cultured at 37°C for 3 to 4 days. This stimulation cycle was performed a total of 3 times. Finally, multimerization was performed by staining with Live/dead-Aqua dye (Invitrogen, Karlsruhe, Germany), CD8-FITC antibody clone SK1 (BD, Heidelberg, Germany) and PE- or APC-coupled A*2402MHC multimer staining body analysis. For analysis, a BD LSRII SORP cytometer equipped with appropriate lasers and screening procedures was used. Peptide-specific cells were calculated as a percentage of total CD8+ cells. Multimer analysis results were evaluated using FlowJo software (Tree Star, Oregon, USA). In vitro packing of specific multimer+ CD8+ lymphocytes was detected using appropriate gating techniques and compared to negative control stimulated groups. If at least one evaluable in vitro stimulated well in a healthy donor is found to contain a specific CD8+ T cell line after in vitro stimulation (i.e. the well contains at least 1% specific multimer+ CD8+ T cells and the specific multimer The percentage of + is at least 10 times the median negative control stimulation), the immunogenicity of a given antigen is tested. In vitro immunogenicity of the IMA941 peptide For 47 of the 54 tested HLA-A*2402 peptides and 3 of the 3 tested HLA-A*0201 peptides, in vitro immunogenicity could be demonstrated by generating peptide-specific T cell lines. Exemplary flow cytometry results after TUMAP-specific multimer staining for two peptides of the invention and corresponding negative controls are shown in FIG. 3 . The results for the 54 A*2402s and 3 A*0201s of the present invention are summarized in Table 4. Table 4: In vitro immunogenicity of HLA class I peptides of the invention The results of the in vitro immunogenicity experiments performed by Immatics show the percentage of positive tested donors and wells evaluated. At least four donors and 48 plate wells were evaluated for each peptide. SEQ ID NO: antigen Positive donor/tested donor [%] Positive wells/tested wells [%] 1 CDC2-001 83 28 2 ASPM-002 67 32 18 MMP3-001 11 1 4 MET-006 67 twenty one 3 UCHL5-001 75 12 7 MST1R-001 50 13 33 KIF2C-001 17 2 9 SMC4-001 73 10 17 EPHA2-005 0 0 5 PROM1-001 83 26 6 MMP11-001 33 11 8 NFYB-001 50 7 16 ASPM-001 17 3 20 PLK4-001 60 5 14 ABL1-001 83 18 26 ATAD2-001 33 3 twenty one ATAD2-002 17 1 27 ATAD2-003 0 0 12 AVL9-001 100 31 twenty two COL12A1-001 0 0 twenty three COL6A3-001 0 0 twenty four FANCI-001 17 1 28 HSP90B1-001 50 7 15 MUC6-001 83 twenty two 13 NUF2-001 100 50 19 NUF2-002 50 6 11 PPAP2C-001 83 29 25 RPS11-001 17 3 29 SIAH2-001 50 8 30 SLC6A6-001 17 1 10 UQCRB-001 83 twenty four 31 IQGAP3-001 100 twenty four 32 ERBB3-001 83 CCDC88A-001 0 0 CCNB1-003 33 3 CCND2-001 17 10 CCNE2-001 0 0 CEA-010 40 3 CLCN3-001 33 6 DNAJC10-001 50 15 DNAJC10-002 33 3 EIF2S3-001 17 1 EIF3L-001 100 29 EPPK1-001 17 1 GPR39-001 50 6 ITGB4-001 67 20 LCN2-001 17 1 SDHC-001 33 3 PBK-001 0 0 POLD3-001 67 7 PSMD14-001 17 1 PTK2-001 17 4 TSPAN1-002 17 1 ZNF598-001 83 17 The following peptides have been described in other Immatics applications and are included in vaccines IMA901 (MET-001 and TOP-001), IMA910 (MET-001 and TOP-001) and IMA950 (IGF2BP3-001). For example, MET-001 can lead to a particularly good in vivo response, and this result can be considered as evidence that the peptides of the invention are clinically useful. SEQ ID NO: antigen Positive donor/tested donor [%] Positive wells/tested wells [%] IGF2BP3-001 50 twenty one MET-001 67 42 TOP-001 40 10 The results of the in vitro immunogenicity experiments performed show the percentage of positive tested donors and wells evaluated. At least four donors and 48 plate wells were evaluated for each peptide. references Ahmed, A. U., et al. "Effect of disrupting seven-in-absentia homolog 2 function on lung cancer cell growth."J Natl. Cancer Inst. 100.22 (2008): 1606-29. Allison, J. P. and M. F. Krummel. "The Yin and Yang of T cell costimulation."Science 270.5238 (1995): 932-33. Altmeyer, A., et al. "Tumor-specific cell surface expression of the-KDEL containing, endoplasmic reticular heat shock protein gp96."Int J Cancer 69.4 (1996): 340-49. Appay, V., et al. "Decreased specific CD8+ T cell cross-reactivity of antigen recognition following vaccination with Melan-A peptide."Eur. J Immunol. 36.7(2006): 1805-14. Banerjee, S. K., et al. "Expression of cdc2 and cyclin B1 in Helicobacter pylori-associated gastric MALT and MALT lymphoma : relationship to cell death, proliferation, and transformation."Am J Pathol. 156.1 (2000): 217-25. Bartman, A. E., et al. "Aberrant expression of MUC5AC and MUC6 gastric mucin genes in colorectal polyps."Int J Cancer 80.2 (1999): 210-18. Basu, S., et al. "Necrotic but not apoptotic cell death releases heat shock proteins, which deliver a partial maturation signal to dendritic cells and activate the NF-kappa B pathway."Int Immunol. 12.11(2000): 1539-46. Bauer, B., S. Bartfeld, and T. F. Meyer. "H. pylori blocks EGFR endocytosis via the non-receptor selectively kinase c-Abl and CagA."Cell Microbiol. 11.1(2009): 156-69. Benatti, P., et al. "A balance between NF-Y and p53 governs the pro- and anti-apoptotic transcriptional response."Nucleic Acids Res 36.5(2008): 1415-28. Bertolini, G., et al. "Highly tumorigenic lung cancer CD133+ cells display stem-like features and are spared by cisplatin treatment."Proc Natl.Acad.Sci.USA 106.38 (2009): 16281-86. Bierie, B. and H. L. Moses. "TGF-beta and cancer."Cytokine Growth Factor Rev. 17.1-2 (2006): 29-40. Bitoun, E. and K. E. Davies. "The robotic mouse: unravelling the function of AF4 in the cerebellum."Cerebellum. 4.4 (2005): 250-60. Bolhassani, A. and S. Rafati. "Heat-shock proteins as powerful weapons in vaccine development."Expert.Rev.Vaccines. 7.8(2008): 1185-99. Borset, M., et al. "The role of hepatocyte growth factor and its receptor c-Met in multiple myeloma and other blood malignancies."Leuk.Lymphoma 32.3-4 (1999): 249-56. Bradbury, P. A., et al. "Matrix metalloproteinase 1, 3 and 12 polymorphisms and esophageal adenocarcinoma risk and prognosis."Carcinogenesis 30.5(2009): 793-98. Brown, C. E., et al. "Recognition and killing of brain tumor stem-like initiating cells by CD8+ cytolytic T cells."Cancer Research 69.23 (2009): 8886-93. Bruckdorfer, T., O. Marder, and F. Albericio. "From production of peptides in milligram amounts for research to multi-tons quantities for drugs of the future."Curr.Pharm.Biotechnol. 5.1(2004): 29-43. Brunsvig, P. F., et al. "Telomerase peptide vaccination: a phase I/II study in patients with non-small cell lung cancer."Cancer Immunol. Immunoother. 55.12(2006): 1553-64. Cabanes, D., et al. "Gp96 is a receptor for a novel Listeria monocytogenes virulence factor, Vip, a surface protein."EMBO J 24.15(2005): 2827-38. Calzado, M. A., et al. "An inducible autoregulatory loop between HIPK2 and Siah2 at the apex of the hypoxic response."Nat.Cell Biol. 11.1 (2009): 85-91. Castelli, C., et al. "Heat shock proteins: biological functions and clinical application as personalized vaccines for human cancer."Cancer Immunol. Immunoother. 53.3 (2004): 227-33. Castriconi, R., et al. "Both CD133+ and C."Eur. J Immunol. 37.11(2007): 3190-96. Chanock, S. J., et al. "HLA-A, -B, -Cw, -DQA1 and -DRB1 Alleles in a Caucasian Population from Bethesda, USA."Hum. Immunol. 65(2004): 1211-23. Chen, C. H., et al. "Inhibition of heregulin signaling by an aptamer that preferentially binds to the oligomeric form of human epidermal growth factor receptor-3."Proc Natl.Acad.Sci.USA 100.16 (2003): 9226-31. Chen, Z. and J. J. O'Shea. "Regulation of IL-17 production in human lymphocytes."Cytokine 41.2 (2008): 71-78. Cho, S. O., et al. "Helicobacter pylori in a Korean Isolate Expressed Proteins Differentially in Human Gastric Epithelial Cells."Dig.Dis.Sci. (2009). Christianson, J. C., et al. "OS-9 and GRP94 deliver mutant alpha1-antitrypsin to the Hrd1-SEL1L ubiquitin ligase complex for ERAD."Nat.Cell Biol. 10.3 (2008): 272-82. Cisek, L. J. and J. L. Corden. "Phosphorylation of RNApolymerase by the murine homologue of the cell-cycle control protein cdc2."Nature 339.6227 (1989): 679-84. Colombetti, S., et al. "ProlongedTCR/CD28 engagement drives IL-2-independent T cell clonal expansion through signaling mediated by the mammalian target of rapamycin."J Immunol. 176.5 (2006): 2730-38. Confalonieri, S., et al. "Alterations of ubiquitin ligases in human cancer and their association with the natural history of the tumor."Oncogene 28.33(2009): 2959-68. Corso, S., et al. "Silencing the MET oncogene leads to regression of experimental tumors and metastases."Oncogene 27.5 (2008): 684-93. Cox, C. V., et al. "Expression of CD133 on leukemia-initiating cells in childhood ALL."blood 113.14 (2009): 3287-96. Cunha-Ferreira, I., et al. "The SCF/Slimb ubiquitin ligase limits centrosome amplification through degradation of SAK/PLK4."Curr.Biol. 19.1(2009): 43-49. DeLuca, J. G., et al. "Hec1 and nuf2 are core components of the kinetochore outer plate essential for organizing microtubule attachment sites."Mol.Biol.Cell 16.2 (2005): 519-31. Deng, H., et al. "Matrix metalloproteinase 11 depletion inhibits cell proliferation in gastric cancer cells."Biochem.Biophys.Res Commun. 326.2 (2005): 274-81. Dengjel, J., et al. "Unexpected Abundance of HLA ClassIIPresented Peptides in Primary Renal Cell Carcinomas."Clin Cancer Res. 12.14(2006): 4163-70. Deremer, D. L., C. Ustun, and K. Natarajan. "Nilotinib: a second-generation tyrosine kinase inhibitor for the treatment of chronic myelogenous leukemia."Clin Ther. 30.11(2008): 1956-75. Di Renzo, M. F., et al. "Overexpression and amplification of the met/HGF receptor gene during the progression of colorectal cancer."Clin.Cancer Res. 1.2 (1995): 147-54. Dong, G., et al. "Hepatocyte growth factor/scatter factor-induced activation of MEK and PI3K signal pathways contributes to expression of proangiogenic cytokines interleukin-8 and vascular endothelial growth factor in head and neck squamous cell carcinoma."Cancer Res. 61.15 (2001): 5911-18. Dudley, M. E., et al. "Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes."Science 298.5594 (2002): 850-54. Dudley, M. E., et al. "Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma."J.Clin.Oncol. 23.10(2005): 2346-57. Duong, C., et al. "Pretreatment gene expression profiles can be used to predict response to neoadjuvant chemoradiotherapy in esophageal cancer."Ann Surg Oncol 14.12(2007): 3602-09. Egland, K. A., et al. "High expression of a cytokeratin-associated protein in many cancers." ProcNatl.Acad.Sci.USA 103.15 (2006): 5929-34. Eramo, A., et al. "Identification and expansion of the tumorigenic lung cancer stem cell population."Cell Death Differ 15.3 (2008): 504-14. Esashi, F., et al. "CDK-dependent phosphorylation of BRCA2 as a regulatory mechanism for recombinational repair."Nature 434.7033 (2005): 598-604. Escobar, M. A., et al. "Profiling of nuclear extract proteins from human neuroblastoma cell lines: the search for fingerprints."J Pediatr.Surg 40.2 (2005): 349-58. Ferracini, R., et al. "The Met/HGF receptor is over-expressed in human osteosarcomas and is activated by either a paracrine or an autocrine circuit."Oncogene 10.4 (1995): 739-49. Fischer, J., et al. "Duplication and overexpression of the mutant allele of the MET proto-oncogene in multiple hereditary papillary renal cell tumours."Oncogene 17.6 (1998): 733-39. Flanagan, J. M., et al. "Genomics screen in transformed stem cells reveals RNASEH2A, PPAP2C, and ADARB1 as putative anticancer drug targets."Mol. Cancer Ther. 8.1(2009): 249-60. Fong, L., et al. "Altered peptide ligand vaccination with Flt3 ligand expanded dendritic cells for tumor immunotherapy."Proc.Natl.Acad.Sci.USA 98.15 (2001): 8809-14. Frasor, J., et al. "Estrogen down-regulation of the corepressor N-CoR: mechanism and implications for estrogen derepression of N-CoR-regulated genes."Proc Natl.Acad.Sci.USA 102.37 (2005): 13153-57. Frew, I. J., et al. "Generation and analysis of Siah2 mutant mice."Mol.Cell Biol. 23.24(2003): 9150-61. Fu, Y. and A. S. Lee. "Glucose regulated proteins in cancer progression, drug resistance and immunotherapy."Cancer Biol. Ther. 5.7(2006): 741-44. Furge, K. A., et al. "Suppression of Ras-mediated tumorigenicity and metastasis through inhibition of the Met receptor tyrosine kinase."Proc.Natl.Acad.Sci.USA 98.19 (2001): 10722-27. Furge, K. A., Y. W. Zhang, and G. F. Vande Woude. "Met receptor tyrosine kinase: enhanced signaling through adapter proteins."Oncogene 19.49 (2000): 5582-89. Gattinoni, L., et al. "Adoptive immunotherapy for cancer: building on success."Nat. Rev. Immunol. 6.5(2006): 383-93. Gherardi, E. and M. Stoker. "Hepatocyte growth factor--scatter factor: mitogen, motogen, and met."Cancer Cells 3.6 (1991): 227-32. Glen, A., et al. "iTRAQ-facilitated proteomic analysis of human prostate cancer cells identifies proteins associated with progression."J Proteome.Res 7.3 (2008): 897-907. Gnjatic, S., et al. "NY-CO-58/KIF2C is overexpressed in a variety of solid tumors and induces frequent T cell responses in patients with colorectal cancer."Int J Cancer (2009). Guo, W. C., et al. "Expression and its clinical significance of heat shock protein gp96 in human osteosarcoma."Neoplasma 57.1 (2010): 62-67. Habelhah, H., et al. "Stress-induced decrease in TRAF2 stability is mediated by Siah2."EMBO J 21.21 (2002): 5756-65. Hamamoto, A., et al. "Aberrant expression of the gastric mucin MUC6 in human pulmonary adenocarcinoma xenografts."Int J Oncol 26.4 (2005): 891-96. Harada, T., et al. "Genome-wide analysis of pancreatic cancer using microarray-based techniques."Pancreatology. 9.1-2(2009): 13-24. Harper, L. J., et al. "Stem cell patterns in cell lines derived from head and neck squamous cell carcinoma."J Oral Pathol. Med 36.10(2007): 594-603. Hayama, S., et al. "Activation of CDCA1-KNTC2, members of centromere protein complex, involved in pulmonary carcinogenesis."Cancer Research 66.21(2006): 10339-48. Hayashi, M., et al. "High expression of HER3 is associated with a decreased survival in gastric cancer."Clinical Cancer Research 14.23(2008): 7843-49. Heike, M., et al. "Expression of stress protein gp96, a tumor rejection antigen, in human colorectal cancer."Int J Cancer 86.4 (2000): 489-93. Hodorova, I., et al. "Gp96 and its different expression in breast carcinomas."Neoplasma 55.1 (2008): 31-35. Horton, R. A., et al. "A substrate for deubiquitinating enzymes based on time-resolved fluorescence resonance energy transfer between terbium and yellow fluorescent protein."Anal.Biochem. 360.1 (2007): 138-43. House, C. M., A. Moller, and D. D. Bowtell. "Siah proteins: novel drug targets in the Ras and hypoxia pathways."Cancer Research 69.23(2009): 8835-38. Howard, E. W., et al. "Decreased adhesiveness, resistance to anoikis and suppression of GRP94 are integral to the survival of circulating tumor cells in prostate cancer."Clin Exp.Metastasis 25.5 (2008): 497-508. Hu, G. and E. R. Fearon. "Siah-1 N-terminal RING domain is required for proteolysis function, and C-terminalSEQuences regulate oligomerization and binding to target proteins."Mol.Cell Biol. 19.1 (1999): 724-32. Huang, Y., et al. "Characterization of GPR56 protein and its suppressed expression in human pancreatic cancer cells."Mol. Cell Biochem. 308.1-2 (2008): 133-39. Jansen, M. P., et al. "Downregulation of SIAH2, an ubiquitin E3 ligase, is associated with resistance to endocrine therapy in breast cancer."Breast Cancer Res Treat. 116.2 (2009): 263-71. Jia, H. L., et al. "Gene expression profiling reveals potential biomarkers of human hepatocellular carcinoma."Clinical Cancer Research 13.4(2007): 1133-39. Jucker, M., et al. "The Met/hepatocyte growth factor receptor(HGFR) gene is overexpressed in some cases of human leukemia and lymphoma."Leuk.Res. 18.1 (1994): 7-16. Jung, G., J. A. Ledbetter, and H. J. Muller-Eberhard. "Induction of cytotoxicity in resting human T lymphocytes bound to tumor cells by antibody heteroconjugates."Proc Natl Acad Sci USA 84.13 (1987): 4611-15. Jung, H. M., S. J. Choi, and J. K. Kim. "Expression profiles of SV40-immortalization-associated genes upregulated in various human cancers."J Cell Biochem. 106.4(2009): 703-13. Kaneko, N., et al. "siRNA-mediated knockdown against CDCA1 and KNTC2, both frequently overexpressed in colorectal and gastric cancers, suppresses cell proliferation and induces apoptosis."Biochem.Biophys.Res Commun. 390.4 (2009): 1235-40. Kang, H. M., et al. "Effects of Helicobacter pylori Infection on gastric mucin expression."J Clin Gastroenterol. 42.1(2008): 29-35. Ko, M. A., et al. "Plk4 haploinsufficiency causes mitotic infidelity and carcinogenesis."Nat.Genet. 37.8 (2005): 883-88. Kobayashi, M., et al. "Activation of ErbB3-PI3-kinase pathway is correlated with malignant phenotypes of adenocarcinomas."Oncogene 22.9 (2003): 1294-301. Koochekpour, S., et al. "Met and hepatocyte growth factor/scatter factor expression in human gliomas."Cancer Res. 57.23 (1997): 5391-98. Korzeniewski, N., et al. "Cullin 1 functions as a centrosomal suppressor of centriole multiplication by regulating polo-like kinase 4 protein levels."Cancer Research 69.16 (2009): 6668-75. Krieg, A. M. "Therapeutic potential of Toll-like receptor 9 activation."Nat. Rev. Drug Discov. 5.6(2006): 471-84. Kunimoto, K., et al. "Involvement of IQGAP3, a regulator of Ras/ERK-related cascade, in hepatocyte proliferation in mouse liver regeneration and development."J Cell Physiol 220.3 (2009): 621-31. Kuriyama, R., et al. "Gamma-tubulin-containing abnormal centrioles are induced by insufficient Plk4 in human HCT116 colorectal cancer cells."J Cell Sci. 122. Pt 12(2009): 2014-23. Lee, H. S., et al. "MUC1, MUC2, MUC5AC, and MUC6 expressions in gastric carcinomas: their roles as prognostic indicators."Cancer 92.6 (2001): 1427-34. Leivo, I., et al. "Characterization of gene expression in major types of salivary gland carcinomas with epithelial differentiation."Cancer Genet. Cytogenet. 156.2 (2005): 104-13. Lemmel, C., et al. "Differential quantitative analysis of MHCligands by mass spectrometry using stable isotope labeling."Nat.Biotechnol. 22.4 (2004): 450-54. Li, G., et al. "Downregulation of E-cadherin and Desmoglein 1 by autocrine hepatocyte growth factor during melanoma development."Oncogene 20.56 (2001): 8125-35. Lim, S. O., et al. "Expression of heat shock proteins (HSP27, HSP60, HSP70, HSP90, GRP78, GRP94) in hepatitis B virus-related hepatocellular carcinomas and dysplastic nodules."World J Gastroenterol. 11.14(2005): 2072-79. Lin, W., et al. "Tyrosine kinases and gastric cancer."Oncogene 19.49 (2000): 5680-89. Liu, B. and Z. LI. "Endoplasmic reticulum HSP90b1 (gp96, grp94) optimizes B-cell function via chaperoning integrin and TLR but not immunoglobulin."blood 112.4 (2008): 1223-30. Liu, S. Y., et al. "Requirement of MMP-3 in anchorage-independent growth of oral squamous cell carcinomas."J Oral Pathol. Med 36.7(2007): 430-35. Lochter, A., et al. "The significance of matrix metalloproteinases during early stages of tumor progression."Ann NYAcad. Sci. 857(1998): 180-93. Lund, C. V., et al. "Zinc finger transcription factors designed for bispecific coregulation of ErbB2 and ErbB3 receptors: insights into ErbB receptor biology."Mol.Cell Biol. 25.20(2005): 9082-91. Ma, S., et al. "Identification and characterization of tumorigenic liver cancer stem/progenitor cells."Gastroenterology 132.7 (2007): 2542-56. MacLeod, R. J., M. Hayes, and I. Pacheco. "Wnt5a secretion stimulated by the extracellular calcium-sensing receptor inhibits defective Wnt signaling in colon cancer cells."Am J Physiol Gastrointest. Liver Physiol 293.1 (2007): G403-G411. Macmillan, J. C., et al. "Comparative expression of the mitotic regulators SAK and PLK in colorectal cancer."Ann Surg Oncol 8.9 (2001): 729-40. Maney, T., et al. "The kinetochore of higher eucaryotes: a molecular view."Int Rev. Cytol. 194(2000): 67-131. Martin, C. M., et al. "Gene expression profiling in cervical cancer: identification of novel markers for disease diagnosis and therapy."Methods Mol.Biol. 511(2009): 333-59. Matsukita, S., et al. "Expression of mucins(MUC1, MUC2, MUC5AC and MUC6) in mucinous carcinoma of the breast: comparison with invasive ductal carcinoma."Histopathology 42.1 (2003): 26-36. Maulik, G., et al. "Role of the hepatocyte growth factor receptor, c-Met, in oncogenesis and potential for therapeutic inhibition."Cytokine Growth Factor Rev. 13.1 (2002): 41-59. Mizrak, D., M. Brittan, and M. Alison. "CD133: molecule of the moment."J Pathol . 214.1(2008): 3-9. Montesano, R., et al. "Differential effects of hepatocyte growth factor isoforms on epithelial and endothelial tubulogenesis."Cell Growth Differ. 9.5 (1998): 355-65. Monzani, E., et al. "Melanoma contains CD133 and ABCG2 positive cells with enhanced tumorigenic potential."Eur.J Cancer 43.5 (2007): 935-46. Moore, A. and L. Wordeman. "The mechanism, function and regulation of depolymerizing kinesins during mitosis."Trends Cell Biol. 14.10 (2004): 537-46. Morgan, R. A., et al. "Cancer Regression in Patients After Transfer of Genetically Engineered Lymphocytes."Science (2006). Mori, M., et al. "HLA gene and haplotype frequencies in the North American population: the National Marrow Donor Program Donor Registry."Transplantation 64.7(1997): 1017-27. Murray, G. I., et al. "Matrix metalloproteinases and their inhibitors in gastric cancer."Gut 43.6 (1998): 791-97. Murshid, A., J. Gong, and S. K. Calderwood. "Heat-shock proteins in cancer vaccines: agents of antigen cross-presentation."Expert.Rev.Vaccines. 7.7(2008): 1019-30. Nakaigawa, N., et al. "Inactivation of von Hippel-Lindau gene induces constitutive phosphorylation of MET protein in clear cell renal carcinoma."Cancer Res. 66.7(2006): 3699-705. Nakamura, Y., et al. "Clinicopathological and biological significance of mitotic centromere-associated kinesin overexpression in human gastric cancer."Br.J Cancer 97.4 (2007): 543-49. Nakayama, K., J. Qi, and Z. Ronai. "The ubiquitin ligase Siah2 and the hypoxia response."Mol.Cancer Res 7.4 (2009): 443-51. Naldini, L., et al. "Hepatocyte growth factor(HGF) stimulates the tyrosine kinase activity of the receptor encoded by the proto-oncogene c-MET."Oncogene 6.4 (1991): 501-04. Nguyen, Q. N., et al. "Light controllable siRNAs regulate gene suppression and phenotypes in cells."Biochim.Biophys.Acta 1758.3 (2006): 394-403. Nishio, K., et al. "Crystal structure of the de-ubiquitinating enzyme UCH37(human UCH-L5) catalytic domain."Biochem.Biophys.Res Commun. 390.3 (2009): 855-60. Nojima, H., et al. "IQGAP3 regulates cell proliferation through the Ras/ERK signalling cascade."Nat.Cell Biol. 10.8 (2008): 971-78. Nomura, H., et al. "Enhanced production of matrix metalloproteinases and activation of matrix metalloproteinase 2(gelatinase A) in human gastric carcinomas."Int J Cancer 69.1 (1996): 9-16. Nomura, H., et al. "Network-based analysis of calcium-binding protein genes identifies Grp94 as a target in human oral carcinogenesis."Br.J Cancer 97.6 (2007): 792-801. Ohnuma, S., et al. "Cancer-associated splicing variants of the CDCA1 and MSMB genes expressed in cancer cell lines and surgically resected gastric cancer tissues."Surgery 145.1 (2009): 57-68. Park, Y. H., et al. "Capecitabine in combination with Oxaliplatin(XELOX) as a first-line therapy for advanced gastric cancer."Cancer Chemother.Pharmacol. (2007). Pascolo, S., et al. "The non-classicalHLA class I molecule HFE does not influence the NK-like activity contained in fresh human PBMCs and does not interact with NK cells."Int.Immunol. 17.2 (2005): 117-22. Peel, N., et al. "Overexpressing centriole-replication proteins in vivo induces centriole overduplication and de novo formation."Curr.Biol. 17.10(2007): 834-43. Pereira, M. B., et al. "Immunohistochemical study of the expression of MUC5AC and MUC6 in breast carcinomas and adjacent breast tissues."J Clin Pathol. 54.3 (2001): 210-13. Pietra, G., et al. "Natural killer cells kill human melanoma cells with characteristics of cancer stem cells."Int Immunol. 21.7(2009): 793-801. Poller, D. N., et al. "Production and characterization of a polyclonal antibody to the c-erbB-3 protein: examination of c-erbB-3 protein expression in adenocarcinomas."J Pathol. 168.3 (1992): 275-80. Pons, E., C. C. Uphoff, and H. G. Drexler. "Expression of hepatocyte growth factor and its receptor c-met in human leukemia-lymphoma cell lines."Leuk.Res. 22.9 (1998): 797-804. Ponzetto, C., et al. "A novel recognition motif for phosphatidylinositol 3-kinase binding mediates its association with the hepatocyte growth factor/scatter factor receptor."Mol.Cell Biol. 13.8 (1993): 4600-08. Poppe, M., et al. "Phosphorylation of Helicobacter pylori CagA by c-Abl leads to cell motility."Oncogene 26.24 (2007): 3462-72. Pytel, D., et al. "Tyrosine kinase blockers: new hope for successful cancer therapy."Anticancer Agents Med Chem. 9.1(2009): 66-76. Qi, J., et al. "The ubiquitin ligase Siah2 regulates tumorigenesis and metastasis by HIF-dependent and -independent pathways."Proc Natl.Acad.Sci.USA 105.43 (2008): 16713-18. Qian, C. N., et al. "Met protein expression level correlates with survival in patients with late-stage nasopharyngeal carcinoma."Cancer Res. 62.2 (2002): 589-96. Qian, Z., et al. "Cytogenetic and genetic pathways in therapy-related acute myeloid leukemia."Chem.Biol.Interact. (2009). Ramirez, R., et al. "Over-expression of hepatocyte growth factor/scatter factor(HGF/SF) and the HGF/SF receptor(cMET) are associated with a high risk of metastasis and recurrence for children and young adults with papillary thyroid carcinoma."Clin Endocrinol.(Oxf) 53.5 (2000): 635-44. Rammensee, H. G., et al. "SYFPEITHI: database for MHCligands and peptide motifs."Immunogenetics 50.3-4 (1999): 213-19. Rammensee, H. G., J. Bachmann, and S. Stevanovic.MHCLigands and Peptide Motifs. Springer-Verlag, Heidelberg, Germany, 1997. Rappa, G., O. Fodstad, and A. Lorico. "The stem cell-associated antigen CD133(Prominin-1) is a molecular therapeutic target for metastatic melanoma."Stem Cells 26.12(2008): 3008-17. Richardson, G. D., et al. "CD133, a novel marker for human prostatic epithelial stem cells."J Cell Sci. 117. Pt 16 (2004): 3539-45. Rini, B. I., et al. "Combination immunotherapy with prostatic acid phosphatase pulsed antigen-presenting cells (provenge) plus bevacizumab in patients with serologic progression of prostate cancer after definitive local therapy."Cancer 107.1 (2006): 67-74. Rodrigues-Martins, A., et al. "Revisiting the role of the mother centriole in centriole biogenesis."Science 316.5827 (2007): 1046-50. Rosenberg, S. A., et al. "A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high-dose interleukin-2 alone."N. Engl. J. Med. 316.15 (1987): 889-97. Rosenberg, S. A., et al. "Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report."N.Engl.J Med 319.25 (1988): 1676-80. Rott, R., et al. "Monoubiquitylation of alpha-synuclein by seven in absentia homolog(SIAH) promotes its aggregation in dopaminergic cells."J Biol.Chem. 283.6 (2008): 3316-28. Rutella, S., et al. "Cells with characteristics of cancer stem/progenitor cells express the CD133 antigen in human endometrial tumors."Clinical Cancer Research 15.13 (2009): 4299-311. Saiki, R. K., et al. "Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase."Science 239.4839 (1988): 487-91. Samant, G. V. and P. W. Sylvester. "gamma-Tocotrienol inhibits ErbB3-dependent PI3K/Akt mitogenic signalling in neoplastic mammary epithelial cells."Cell Prolif. 39.6 (2006): 563-74. Sanidas, E. E., et al. "Expression of the c-erbB-3 gene product in gastric cancer."Int J Cancer 54.6 (1993): 935-40. Scott, G. K., et al. "Coordinate suppression of ERBB2 and ERBB3 by enforced expression of micro-RNA miR-125a or miR-125b."J Biol.Chem. 282.2 (2007): 1479-86. Sergina, N. V., et al. "Escape from HER-family tyrosine kinase inhibitor therapy by the kinase-inactive HER3."Nature 445.7126 (2007): 437-41. Shah, M., et al. "Inhibition of Siah2 ubiquitin ligase by vitamin K3(menadione) attenuates hypoxia and MAPK signaling and blocks melanoma tumorigenesis."Pigment Cell Melanoma Res 22.6 (2009): 799-808. Shapiro, G. I. "Cyclin-dependent kinase pathways as targets for cancer treatment."J Clin Oncol 24.11(2006): 1770-83. Sherman-Baust, C. A., et al. "Remodeling of the extracellular matrix through overexpression of collagen VI contributes to cisplatin resistance in ovarian cancer cells."Cancer Cell 3.4 (2003): 377-86. Sheu, M. L., S. H. Liu, and K. H. Lan. "Honokiol induces calpain-mediated glucose-regulated protein-94 cleavage and apoptosis in human gastric cancer cells and reduces tumor growth."PLoS.ONE. 2.10(2007): e1096. Shimo, A., et al. "Involvement of kinesin family member 2C/mitotic centromere-associated kinesin overexpression in mammary carcinogenesis."Cancer Sci. 99.1(2008): 62-70. Singh, S. K., et al. "Identification of a cancer stem cell in human brain tumors." Cancer Res. 63.18(2003): 5821-28. Singh, S. K., et al. "Identification of human brain tumor initiating cells."Nature 432.7015 (2004): 396-401. Sithanandam, G. and L. M. Anderson. "The ERBB3 receptor in cancer and cancer gene therapy."Cancer Gene Ther. 15.7(2008): 413-48. Sithanandam, G., et al. "Inactivation of ErbB3 by siRNA promotes apoptosis and attenuates growth and invasiveness of human lung adenocarcinoma cell line A549."Oncogene 24.11(2005): 1847-59. Skawran, B., et al. "Gene expression profiling in hepatocellular carcinoma: upregulation of genes in amplified chromosome regions."Mod.Pathol. 21.5(2008): 505-16. Slesak, B., et al. "Expression of epidermal growth factor receptor family proteins(EGFR, c-erbB-2 and c-erbB-3) in gastric cancer and chronic gastritis."Anticancer Res 18.4A (1998): 2727-32. Small, E. J., et al. "Placebo-controlled phase III trial of immunologic therapy with sipuleucel-T(APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer."J Clin Oncol. 24.19 (2006): 3089-94. Smith, L. M., et al. "CD133/prominin-1 is a potential therapeutic target for antibody-drug conjugates in hepatocellular and gastric cancers."Br.J Cancer 99.1 (2008): 100-09. Smith, M. J., et al. "Analysis of differential gene expression in colorectal cancer and stroma using fluorescence-activated cell sorting purification."Br.J Cancer 100.9 (2009): 1452-64. Smogorzewska, A., et al. "Identification of the FANCI protein, a monoubiquitinated FANCD2 paralog required for DNArepair."Cell 129.2 (2007): 289-301. Staehler, M., Stenzl, A., Dietrich, P. Y., Eisen, T., Haferkamp, A., Beck, J., Mayer, A., Walter, S., Singh-Jasuja, H., and Stief, C . A phase I study to evaluate safety, immunogenicity and anti-tumor activity of the multi-peptide vaccine IMA901 in renal cell carcinoma patients(RCC). Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I Vol 25, No. 18S( June 20 Supplement), 2007: 5098. 6-20-2007. Ref Type: Abstract Stemmann, O., et al. "Dual inhibition of sister chromatid separation at metaphase." Cell 107.6(2001): 715-26. Suetsugu, A., et al. "Characterization of CD133+ hepatocellular carcinoma cells as cancer stem/progenitor cells."Biochem.Biophys.Res.Commun. 351.4 (2006): 820-24. Suva, M. L., et al. "Identification of Cancer Stem Cells in Ewing's Sarcoma."Cancer Research (2009). Swallow, C. J., et al. "Sak/Plk4 and mitotic fidelity."Oncogene 24.2 (2005): 306-12. Szczepanowski, M., et al. "Regulation of repp86 stability by human Siah2."Biochem.Biophys.Res Commun. 362.2 (2007): 485-90. Tajima, Y., et al. "Gastric and intestinal phenotypic marker expression in early differentiated-type tumors of the stomach: clinicopathologic significance and genetic background."Clinical Cancer Research 12.21(2006): 6469-79. Takaishi, S., et al. "Identification of gastric cancer stem cells using the cell surface marker CD44."Stem Cells 27.5(2009): 1006-20. Takayama, H., et al. "Diverse tumorigenesis associated with aberrant development in mice overexpressing hepatocyte growth factor/scatter factor."Proc.Natl.Acad.Sci.USA 94.2 (1997): 701-06. Teofili, L., et al. "Expression of the c-met proto-oncogene and its ligand, hepatocyte growth factor, in Hodgkin disease."blood 97.4 (2001): 1063-69. Thorsen, K., et al. "Alternative splicing in colon, bladder, and prostate cancer identified by exon array analysis."Mol. Cell Proteomics. 7.7(2008): 1214-24. Tirino, V., et al. "The role of CD133 in the identification and characterisation of tumour-initiating cells in non-small-cell lung cancer."Eur.J Cardiothorac.Surg 36.3 (2009): 446-53. Todaro, M., et al. "Colon cancer stem cells dictate tumor growth and resist cell death by production of interleukin-4."Cell Stem Cell 1.4(2007): 389-402. Topol, L., et al. "Wnt-5a inhibits the canonical Wnt pathway by promoting GSK-3-independent beta-catenin degradation."J Cell Biol. 162.5 (2003): 899-908. Toribara, N. W., et al. "Human gastric mucin. Identification of a unique species by expression cloning."J Biol.Chem. 268.8 (1993): 5879-85. Tsan, M. F. and B. Gao. "Heat shock protein and innate immunity."Cell Mol. Immunol. 1.4 (2004): 274-79. Tuck, A. B., et al. "Coexpression of hepatocyte growth factor and receptor(Met) in human breast carcinoma."Am. J. Pathol. 148.1 (1996): 225-32. Vairaktaris, E., et al. "Association of -1171 promoter polymorphism of matrix metalloproteinase-3 with increased risk for oral cancer."Anticancer Res 27.6B (2007): 4095-100. Vandenbroeck, K., E. Martens, and I. Alloza. "Multi-chaperone complexes regulate the folding of interferon-gamma in the endoplasmic reticulum."Cytokine 33.5 (2006): 264-73. Walter, S., et al. "Cutting edge: predetermined avidity of humanCD8T cells expanded on calibratedMHC/anti-CD28-coated microspheres."J. Immunol. 171.10 (2003): 4974-78. Wang, Q., et al. "Overexpression of endoplasmic reticulum molecular chaperone GRP94 and GRP78 in human lung cancer tissues and its significance."Cancer Detect.Prev. 29.6 (2005): 544-51. Wang, R., et al. "Activation of the Met receptor by cell attachment induces and sustains hepatocellular carcinomas in transgenic mice."J.Cell Biol. 153.5 (2001): 1023-34. Wang, R. Q. and D. C. Fang. "Effects of Helicobacter pylori infection on mucin expression in gastric carcinoma and pericancerous tissues."J Gastroenterol. Hepatol. 21.2 (2006): 425-31. Wang, S., et al. "IQGAP3, a novel effector of Rac1 and Cdc42, regulates neurite outgrowth."J Cell Sci. 120. Pt 4 (2007): 567-77. Wang, X., et al. "Immunolocalisation of heat shock protein 72 and glycoprotein 96 in colonic adenocarcinoma."Acta Histochem. 110.2 (2008): 117-23. Wang, X. P., et al. "Expression and significance of heat shock protein 70 and glucose-regulated protein 94 in human esophageal carcinoma."World J Gastroenterol. 11.3 (2005): 429-32. Wang, X. P., et al. "Correlation between clinicopathology and expression of heat shock protein 70 and glucose-regulated protein 94 in human colonic adenocarcinoma."World J Gastroenterol. 11.7(2005): 1056-59. Wang, X. P., Q. X. Wang, and X. P. Ying. "Correlation between clinicopathology and expression of heat shock protein 72 and glycoprotein 96 in human gastric adenocarcinoma."Tohoku J Exp. Med 212.1 (2007): 35-41. Weinschenk, T., et al. "Integrated functional genomics approach for the design of patient-individual antitumor vaccines."Cancer Res. 62.20(2002): 5818-27. White, C. D., M. D. Brown, and D. B. Sacks. "IQGAPs in cancer: a family of scaffold proteins underlying tumorigenesis."FEBS Lett. 583.12(2009): 1817-24. Wicks, S. J., et al. "Reversible ubiquitination regulates the Smad/TGF-beta signalling pathway."Biochem.Soc Trans. 34. Pt 5 (2006): 761-63. Wicks, S. J., et al. "The deubiquitinating enzyme UCH37 interacts with Smads and regulates TGF-beta signalling."Oncogene 24.54 (2005): 8080-84. Yajima, S., et al. "Expression profiling of fecal colonocytes for RNA-based screening of colorectal cancer."Int J Oncol 31.5 (2007): 1029-37. Yang, L., et al. "IL-21 and TGF-beta are required for differentiation of human T(H)17 cells."Nature (2008). Yang, S., et al. "Molecular basis of the differences between normal and tumor tissues of gastric cancer."Biochim.Biophys.Acta 1772.9 (2007): 1033-40. Yao, D. F., et al. "Abnormal expression of HSP gp96 associated with HBV replication in human hepatocellular carcinoma."Hepatobiliary.Pancreat.Dis.Int 5.3(2006): 381-86. Yasui, W., et al. "Increased expression of p34cdc2 and its kinase activity in human gastric and colonic carcinomas."Int J Cancer 53.1 (1993): 36-41. Yee, C., et al. "Adoptive T cell therapy using antigen-specific CD8+ T cell clones for the treatment of patients with metastatic melanoma: in vivo persistence, migration, and antitumor effect of transferred T cells."Proc.Natl.Acad.Sci.USA 99.25 (2002): 16168-73. Yin, S., et al. "CD133 positive hepatocellular carcinoma cells possess high capacity for tumorigenicity."Int.J Cancer 120.7 (2007): 1444-50. Yokozaki, H., W. Yasui, and E. Tahara. "Genetic and epigenetic changes in stomach cancer."Int Rev. Cytol. 204(2001): 49-95. Yuan, W., et al. "Expression of EphA2 and E-cadherin in gastric cancer: correlated with tumor progression and lymphogenous metastasis."Pathol.Oncol Res 15.3(2009): 473-78. Yuan, W. J., et al. "Over-expression of EphA2 and EphrinA-1 in human gastric adenocarcinoma and its prognostic value for postoperative patients."Dig.Dis.Sci. 54.11(2009): 2410-17. Zaremba, S., et al. "Identification of an enhancer agonist cytotoxic T lymphocyte peptide from human carcinoembryonic antigen."Cancer Res. 57.20 (1997): 4570-77. Zhang, X., R. M. Kedl, and J. Xiang. "CD40 ligation converts TGF-beta-secreting tolerogenic CD4-8-dendritic cells into IL-12-secreting immunogenic ones."Biochem.Biophys.Res Commun. 379.4 (2009): 954-58. Zhang, X. L., et al. "Comparative study on overexpression of HER2/neu and HER3 in gastric cancer."World J Surg 33.10(2009): 2112-18. Zhao, C., et al. "Hedgehog signalling is essential for maintenance of cancer stem cells in myeloid leukaemia."Nature (2009). Zheng, H., et al. "Cell surface targeting of heat shock protein gp96 induces dendritic cell maturation and antitumor immunity."J Immunol. 167.12 (2001): 6731-35. Zheng, H., et al. "MUC6 down-regulation correlates with gastric carcinoma progression and a poor prognosis: an immunohistochemical study with tissue microarrays."J Cancer Res Clin Oncol 132.12 (2006): 817-23. Zheng, H. C., et al. "Overexpression of GRP78 and GRP94 are markers for aggressive behavior and poor prognosis in gastric carcinomas."Hum.Pathol. 39.7(2008): 1042-49. Zhou, G., et al. "2D differential in-gel electrophoresis for the identification of esophageal scans cell cancer-specific protein markers."Mol. Cell Proteomics. 1.2 (2002): 117-24. Zhou, L., et al. "TGF-beta-induced Foxp3 inhibits T(H)17 cell differentiation by antagonizing RORgammat function."Nature 453.7192(2008): 236-40. Zhu, K. J., et al. "Imiquimod inhibits the differentiation but enhances the maturation of human monocyte-derived dendritic cells."Int Immunopharmacol. 9.4(2009): 412-17.

Figure 1: Representative mass spectrometry demonstrating CDC2-001 presentation in primary tumor sample GC2464. NanoESI-LCMS was performed on a pool of peptides eluted from GC sample 2464. A) Mass chromatogram m/z 597.3501 ± 0.001 Da, z=2 shows that the peptide peaked at retention time 151.63 minutes. B) A peak was detected at 151.63 minutes in the mass chromatogram showing that the signal was m/z 597.3501 in the MS spectrum. C) The collision-induced decay mass spectrum of the selected precursor recorded at the indicated retention time in the nanoESI-LCMS experiment was m/z 597.3501, confirming the presentation of CDC2-001 in the GC2464 tumor sample. D) The fragmentation pattern of the synthetic CDC2-001 reference peptide was recorded and compared with the natural TUMAP fragmentation pattern shown in C to verify the sequence. Figure 2: mRNA expression profiles of selected proteins in normal tissues and 25 gastric cancer samples a) CDC2 (Probeset ID: 203213_at) b) ASPM (Probeset ID: 219918_s_at) Figure 3: Typical results of class I TUMAP peptide-specific in vitro immunogenicity. CD8+ T cells were introduced with artificial antigen-presenting cells loaded with related (left panel) and unrelated peptides (on panel), respectively. After 3 cycles of stimulation, peptide-reactive cells were detected by double staining of correlated and uncorrelated A*2402-multimers. The indicated cells were gated on live CD8+ lymphocytes and the figures represent the percentage of multimer positive cells.

Claims (22)

A peptide consisting of the amino acid sequence of SEQ ID NO: 58, or a pharmaceutically acceptable salt thereof. The peptide of claim 1, which has the ability to bind to human major histocompatibility complex (MHC) class I molecules. The peptide of claim 1, wherein the peptide comprises a non-peptide bond. The peptide of claim 1, wherein the peptide is part of a fusion protein comprising the N-terminal amino acid of the HLA-DR antigen-associated invariant chain (Ii). A nucleic acid encoding the peptide of claim 1 or 4. The nucleic acid of claim 5, which is DNA, cDNA, PNA, RNA, or a combination thereof. An expression vector capable of expressing the nucleic acid of claim 5 or 6. The peptide of any one of claims 1 to 4 for use as a medicament. The nucleic acid according to claim 5 or 6, which is used as a medicine. According to the expression vector of claim 7, it is used as a medicine. A host cell comprising the nucleic acid of claim 5 or 6 or the expression vector of claim 7. The host cell of claim 11, wherein the cell is an antigen presenting cell. The host cell of claim 12, wherein the antigen presenting cell is a dendritic cell. A method of preparing a peptide according to claim 1 or 4, the method comprising culturing a host cell according to any one of claims 11 to 13, and isolating the peptide from the host cell or its culture medium. A method for preparing activated cytotoxic T lymphocytes (CTL) in vitro, the method comprising contacting the CTL in vitro with antigen-loaded human class I MHC molecules expressed on the surface of a suitable antigen-presenting cell for a sufficient period of time, The CTL is thereby activated in an antigen-specific manner, wherein the antigen is a peptide as claimed in claim 1 . The method of claim 15, wherein the antigen presenting cell comprises an expression vector expressing the peptide of claim 1. An activated cytotoxic T lymphocyte (CTL) prepared according to the method of claim 15 or 16, which lymphocyte selectively recognizes an abnormality as claimed in claim 15 1 of peptide cells. A use of a cytotoxic T lymphocyte (CTL) according to claim 17 for the preparation of a medicament for the treatment of cancer cells in a patient, wherein the cancer cells present the peptide according to claim 1 . A peptide according to any one of claims 1 to 4, a nucleic acid according to claim 5 or 6, an expression vector according to claim 7, a cell according to any one of claims 11 to 13 or an activation according to claim 17 Use of the cytotoxic T lymphocytes for the manufacture of a medicament for the treatment of cancer. Use as claimed in claim 19, wherein the medicament is a vaccine. The use of claim 19 or 20, wherein the cancer is gastric cancer, gastrointestinal cancer, colorectal cancer, pancreatic cancer, lung cancer or kidney cancer. A non-medical use of the peptide of claim 1 for the generation and development of specific antibodies against MHC/peptide complexes comprising the peptide.

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